Cerebral Blood Flow

Ischemia

- Lack of oxygen & glucose - Prevents removal of toxic metabolites e.g. lactic acid

What are the 3 main arteries that supply the spinal cord, where do arise from, and what do they supply? What about below the cervical region?

1. Anterior spinal artery (formed by 2 branches of the vertebral artery) - supplies anterior 2/3 of the cord (mainly motor area) 2 & 3. Two posterior spinal arteries (arise from the PICA). - supplies the posterior 1/3 of the cord (mainly sensory area) Below the cervical region this central supply is supplemented by a peripheral system of radially arranged radicular arteries that arise from the aorta • Disruption of blood flow through these radicular arteries, such as during aortic aneurysm repair, can lead to spinal cord infarction and paraplegia

The cerebellum is supplied by branches of what 2 arteries?

1. Basilar artery -Superior cerebellar a. - Anterior inferior cerebellar artery (AICA) 2. Vertebral artery - PICA

Focal ischemia causes: (all are non-mass lesions)

1. Blood vessel disease e.g. Artherosclerosis, HTN, TIA 2. Cardiac disease e.g. A-fib, arrhythmia, mural thrombosis, endocarditis, valve disorders 3. Hematological disorders e.g. sick cell, thrombocytosis

Functions of cerebrospinal fluid

1. Communicates with brain interstitial fluid to maintain a constant extracellular environment for brain cells; importantly, helps to remove metabolites. 2. Buoyancy for the brain & spinal cord to reduce traction on nerve and blood vessels connected with CNS 3. Cushioning effect dampens effects of trauma 4. pH affects pulmonary ventilation and cerebral blood flow

Ependymal cells and their epithelial derivatives of the choroid plexus have several important functions:

1. In the ventricle ependymal cells possess tiny hairlike structures called cilia on their surfaces facing the open space of the cavities they line. The cilia beat in a coordinated pattern to influence the direction of flow of cerebrospinal fluid (CSF), bringing nutrients and other substances to neurons and filtering out molecules that may be harmful to the cells. 2. The beating of ependymal cilia also facilitates distribution of NTMs and other chemical messengers to neurons 3. Primary function of ependymal-derived cells surrounding the blood vessels of the choroid plexus functions mainly to produce CSF. This is accomplished through the selective uptake of water and certain other molecules from the blood into the cells. The substances are then transported across the cells and are secreted into the lateral ventricles in the form of CSF.

Focal hemorrhagic stroke causes:

1. Intracerebral (Mass effect) e.g. Arteriovenous malformation, Berry aneurysm, chronic HTN, trauma, drug abuse 2. Extracerebral e.g. SAH (non-mass lesion), aneurysm, EDH (Mass effect) 3. Hematological Disorders (non-mass lesion) e.g. Hemophilia, anti-coag drugs

• The high metabolic rate of the brain requires a constant supply of nutrients & oxygen and depends on precise regulation of cerebral blood flow (CBF) • Control of CBF involves multiple overlapping regulatory mechanisms The 4 principle regulators of CFB are:

1. Partial pressure of arterial CO2 (PaCO2) 2. MAP 3. Cerebral metabolism 4. ANS

Time course of pathophysiological changes occurring in ischaemic stroke. Excitotoxic mechanisms damage both neurons & glial cells & contribute to the genesis of inflammation & cell death. Exitotoxicity (minutes-hours). Inflammation & edema ( hours). Apoptosis (hours-days). The events that occur in ischemic stroke are?

1. With hypoxia, ATP levels decline & ATP-dependent pumps in neuronal & glial cells become dysfunctional. 2. Na+ leaks into cells. This results in water influx, cell swelling, & cell death. 3. Pumps that remove the glutamate from the synaptic cleft fail, leading to: - further depolarization and neuronal hyperexcitability - Ca++ overload in postsynaptic neurons - formation of destructive free radicals leading to cell death. 4. Increased intracellular Ca++ triggers - inflammatory pathways also caspases that lead to apoptosis of brain cells, particularly in penumbra region- slower mechanism that occurs hours to days after initial focal ischemic event.

What % of CO does the brain receive?

15%

High metabolic rate of the brain

2% of body mass, but consumes 20% of body energy at rest. At rest, 7.5x metabolism/unit mass of tissue compared with non-nervous system tissue.

Brainstem Strokes: Rule of 4's

4 CN in each section (Midbrain, Pons, Medulla). CN that divide evenly into 12--> MIDLINE. (3,4, 6, 12) CN that do NOT divide evenly into 12 --> LATERAL. (5,7,8,9,10,11) 4 Motor syndromes are Midline: 1. Medial Longitudinal Fasciculus (Eye Motor) 2. Motor tract of the UMN (Corticospinal Tract) 3. Medial Lemniscus (Proprioception/Vibration) 4. Motor Nuclei of CN (that divide evenly into 12) 3 Sensory Syndromes are Side (Lateral) 1. Spinothalamic Tract (Pain & temperatrure) 2. Spinocerebellar Tract (RAM) 3. Sympathetic Chain (Dilation, sweating, Horner's syndrome ptosis, anhydrosis) 4. Sensory CN nuclei that do not divide evenly into 12

Cessation of blood supply to the brain for _________________ seconds causes unconsciousness. What happens w/ cessation of blood supply?

5‐10 seconds • In this time neuronal activity declines due to lack of O2 • Irreversible damage to neurons with interruption of blood supply for a few minutes

Gender

<65 years: males > females

Integrated response of neurovascular coupling- 3 processes invoking vasodilation:

A.) Neuronal activity generates Glutamate which activates astrocytes. Astrocytes generate factors directly, or indirectly via the endothelium, that both lead to VASODILATION. Directly- astrocytes have receptors on them for glutamate, which causes a rise in intracellular Ca++ and stimulation of pathways such as COX/arachidonic pathway to generate products that cause direct vasodilation of underlying blood vessel. B.) Factors released by local nerves: e.g. Nitric Oxide, also dilate vasculature. Glutamate can activate other nerves to generate prostaglandins and nitric oxide--> vasodilation. C.) Local factors (from endothelium): e.g. adenosine, K+ invoke vasodilation. In low O2 conditions there is production of acids and adenosine that can directly act on smooth muscle or via astrocyte to cause vasodilation. ***Coupling between activities of the neuron, blood vessel, and astrocyte increases blood flow with increase in neuronal activity.

Extradural hematoma: causative vessel?

ARTERIAL blood collects between the skull and periosteal layer of the dura. Causes a MASS EFFECT. Causative vessel= Middle Meningeal Artery, tearing as a consequence of brain trauma. The dura mater receives its own vasculature; primarily from the middle meningeal artery and vein. It is innervated by the trigeminal nerve (V1, V2 and V3).

How is CSF pressure regulated?

Arachnoid villi. *If resorption of CSF is impaired---> pressure INCREASES. e.g. Fibrosis or blockage impairing arachnoidal villi function; tumour blocking CSF pathways

BBB exists in all areas of the brain except:

Areas known as the circumventricular organs: Hypothalamus, Posterior Pituitary, & area postrema (vomiting centre). These areas: • Lack tight junctions between endothelial cells • Contain sensory receptors that respond to: changes in specific aspects of body fluids e.g. osmolarity, glucose, receptors for hormones that regulate thirst, poisons (area postrema). These areas a re very important for the sampling of blood.

Where do cerebral aneurysms typically occur?

At the bifurcation of the large arteries at the base of the brain; the vast majority are located in the anterior circle of Willis.

Where are dural venous sinuses located?

Between the 2 layers of dura mata and do NOT contain valves.

Contraceptive pill

Blood more likely to clot; ↑ BP

Subarachnoid hemorrhage

Blood vessel on surface of brain bleeds into subarachnoid space (between brain & meninges) Subdural hematomas are caused more frequently by venous rather than arterial damage and are often self-limiting because of the slow bleeding process. Usually non-mass effect However, if the hematoma is large, mass pressure effect may take place, shifting cerebral structures and causing edema in the parenchyma of the brain.

Pt has diffuse (global) motor weakness. (Weak on entire side of body)

Brainstem stroke If it is a focal deficit it will be a cortical stroke.

The peak of cell death resulting from excitotoxicity occurs from

Ca2+ overload in postsynaptic neurons & formation of destructive free radicals leading to cell death Interventions aimed at restoring blood flow to the penumbra region are important in trying to limit the extent of blood damage resulting from intracellular Ca++ inflammatory processes and capsase apoptosis.

Haematological disorders

Conditions that lead to thickening or thinning of blood, or prone to clot formation

Effect of hypoxia on cerebrovascular resistance?

Decreaseses resistance, increases CBF. Decreases resistance by increasing the probability of opening K+ channels (hyperpolarize) in the smooth muscle of cerebral arteries--> vasodilation--> increase in CBF.

The ependymal cells in the ventricles are loosely joined together by special intercellular adhesion sites called _________________________. The ependymal cells surrounding the choroid plexus are connected by _____________________________________.

Desmosomes- enable the cells to form a nearly continuous epithelial sheet over the surface of the ventricles and spinal canal. Because the junctions between the ependymal cells are loose, CSF is able to diffuse from the ventricles into the central nervous system. Tight junctions. These prevent the leakage of substances and fluids from the blood vessels into the CSF. This protects against the unregulated entry of potentially harmful substances into the ventricles and ultimately the central nervous system.

What forms the BBB?

Endothelial cells of the cerebral microvasculature have tight junctions between them & form the BBB that regulates movement of molecules between blood & interstitial fluid compartments basement membrane, pericytes (smooth muscle-like cells), foot processes of astrocytes also help to compose BBB, but ultimately it is the tight junctions between endothelial cells.

Mechanisms involved in pathophysiological changes of ischemic stroke:

Excitotoxicity, inflammation, programmed cell death

Blood- Cerebrospinal fluid barrier

Formed by the tight junctions between choroid epithelial cells & prevents large molecules from entering CSF

Functional areas associated with the Middle Cerebral artery:

Frontal lobe: PMC (hip to head), Premotor area, frontal eye field Parietal cortex: PSC (hip to head); primary taste cortex Temporal lobe: Primary auditory cortex; primary olfactory cortex Basal ganglia (movement initiation) Optic radiation (vision) Uncus (emotion) Dominant hemisphere: language centers- Wenicke's area (receptive speech) and Broca's area (expressive speech) Non-dominant hemisphere: contralateral awareness of self and surroundings

BBB and Blood-CSF barrier are both permeable to

Generally permeable to H2O, CO, O2, most lipid-soluble substances (e.g. anesthetics, alcohol). Slightly permeable to electrolytes. Impermeable to plasma proteins and large non-lipid soluble organic molecules.

Agents produced as a result of increased neuronal activity __________________CBF:

INCREASE e.g. K+, H+, nitric oxide, adenosine = Neurovascular coupling: local brain perfusion is tightly coupled to cerebral metabolism/neuronal activity e.g. Increase in occipital BF when intense light is shined into cat's eye

Strokes in the spinal cord- vessel occlusion usually occurs where?

In a proximal segmental artery, limited to anterior spinal artery territory (anterior 2/3)- motor. Therefore, dorsal columns- proprioception & discriminative touch are spared.

Ethnic background

Increased risk in Asians, Africans, Afro‐Caribbeans

Most deep veins drain into

Internal cerebral veins and then the straight sinus.

Arachnoid Mater- vascularization? innervation?

It consists of layers of connective tissue, is avascular, and does not receive any innervation. Subarachnoid space contains CSF (cushions the brian). Small projections of arachnoid mater into dura (arachnoid granulations) allow CSF to re-enter circulation via dural venous sinuses.

Pia mater- Vascularisation?

Like the dura, it is HIGHLY VASCULARISED with blood vessels perforating through the membrane to supply the underlying neural tissue. This layer also contains the ***choroid plexus, a network of ***capillaries and ***ependyma (specialized ciliated epithelial tissue) that produce cerebrospinal fluid. The pia mater is located underneath the sub-arachnoid space. It is very thin, and tightly adhered to the surface of the brain and spinal cord. It is the only covering to follow the contours of the brain (the gyri and fissures).

Pt has no proprioception and vibration

Medical lemniscus is involved so it is a midline stroke.

Meningitis - 2 most common causative agents - Results

Neisseria meningitidis and Streptococcus pneumoniae. The immune response to the infection causes cerebral oedema, consequently raising intra-cranial pressure. This has two main effects: • Part of the brain can be forced out of the cranial cavity - this is known as cranial herniation. • In combination with systemic hypotension, raised intracranial pressure reduces cerebral perfusion. Both of these complications rapidly result in death.

Astrocytes (astroglial cells):

Non-neural cells that provide support, protection, and nutrition to neurons. • They surround the blood vessels penetrating the cortex and their foot processes are closely connected to the vascular wall • Products of neuronal activity lead to activation of astrocytes which then evoke vasodilation of cerebral vessels

At what PaO2 does CBF increase?

PaO2 ~ 50mmHg / cerebral tissue PO2 ~ 30mmHg

Functional areas associated with the Anterior cerebral artery:

Paracentral lobule: PMC and PSC regions to hip & feet Supplementary motor area (movement) Prefrontal and orbitofrontal cortex (cognition and emotion) Corpus callosum Septal nucleus (pleasure)

PET

Positron Emission Tomography Unstable radio labelled substance is injected into blood stream and concentrate in areas of high regional blood flow. Radioactive decay of tracer is monitored (low spatial resolution).

Territories of the cerebral arteries and the primary motor and sensory cortex

Posterior cerebral artery does not supply PMC. ACA supplies the trunk, leg, and food w/ motor from PMC (precentral gyrus), and sensory from PSC (postcentral gyrus). MCA supplies the arm, hand, face and tongue w/ motor and sensory.

Vascular inflammatory disorders

Promote platelet adhesion on damaged arterial walls

Pt only has motor abnormalities in left leg..

Right ACA is stroked because signals decussate and present on the opposite side.

Branches of the ECA

Some Anatomists Like Freaking Out Poor Medical Students S: superior thyroid artery A: ascending pharyngeal artery L: lingual artery F: facial artery O: occipital artery P: posterior auricular artery M: maxillary artery S: superficial temporal artery

Many substances required for brain function need to be transported across brain endothelial and choroid epithelial cell surfaces. How is this done?

Specific exchangers and transporters for delivery of energy substrates (e.g. glucose via GLUT1), peptides, essential amino acids to brain, and for removing metabolites.

Most superficial veins drain into

Superior sagittal singus

Why is cerebral blood flow so important?

The brain has limited captivity for substrate storage. Neurons have v. limited capacity for anaerobic metabolism. It is highly dependent on oxygen and glucose supply from the Bs. Precise regulation of CBF is essential for maintenance of constant nutrient & oxygen supply. The brain has a high metabolic rate. It is DENSELY vascularized.

How are the anterior & posterior circulations connected?

They are connected together at the base of the midbrain around the optic chiasm. - Form the circle of Willis. -Connections between the circulations allow shunting of blood from anterior to posterior circulations or from one side to the other in the event of an occlusion.

Subdural Hematoma causative vessel?

VENOUS blood collects between the dura and the arachnoid mater. It results from damage to cerebral veins as they empty into the dural venous sinuses.

Functional areas associated with the Posterior cerebral artery:

Visual cortex (primary and association) Hippocampus (long-term memory) Thalamus Hypothalamus (autonomic function)

The brain is perfused because

arterial pressure > intracranial pressure. • The brain is enclosed in the skull & the pressure in this "closed‐ box" acts on the outside of arteries, and opposes arterial pressure • If intracranial pressure increases, blood flow to brain will decrease unless there are compensatory increases in arterial pressure • If intracranial pressure increases further, cerebral perfusion rapidly falls

Age risk factor

b/c of atherosclerosis & arteries less elastic with aging

BOLD MRI

blood oxygen level dependent magnetic resonance imaging: removing O2 from oxyhaemoglobin renders the deoxyhaemoglobin paramagnetic => used to distinguish areas of high metabolic activity Listening to music → ↑metabolism in auditory cortex

Intracerebral hemorrhage (ICH)

blood vessel bursts within brain. Blood may form haematoma within brain parenchyma (Focal Mass effect)

Change in CBF in response to hypoxemia?

causes little change in CBF until a threshold at the steep portion of the oxyhaemoglobin dissociation curve (~80% arterial saturation of O2). • Hypoxia reduces cerebrovascular resistance => ↑CBF

Choroid plexuses

clusters of capillaries that are permeable and allow filtration from the bloodstream to the underlying structures. A layer of ependymal cells connected to each other via tight junctions, forming impermeable layer between leaky capillaries. Any substance that must cross into ventricles must cross through impermeable layer via active transport. Water & unnecessary solutes absorbed by capillary------> CSF forms as a filtrate containing glucose, oxygen, vitamins, and ions (Na+, Cl-, Mg++, etc)

Intraventricular haemorrhage:

common in premature babies of low birth weight Caused by hypoxia produced by pressure on brain during delivery. Causes cell death in walls of the artery and makes them prone to rupture (particularly because these blood vessels are so young and still developing). Bleeding into ventricles.

Arteriovenous malformations:

congenital abnormality resulting in direct communication between arteries and veins (no capillaries); distorted vessels prone to rupture There are no capillaries between cerebral arteries and veins so the high pressure of the arteries is transmitted through to the veins.

Motor Sensory Cortex

contralateral, homunculus, unequal representation

Stroke out the PCA

deficit in vision or language (if it is the dominant hemisphere)

Water & unnecessary solutes absorbed by capillary------> CSF forms as a filtrate containing

glucose, oxygen, vitamins, and ions (Na+, Cl-, Mg++, etc)

Stroke out the MCA

involvement of face

Stroke out the ACA

involvement of leg

CBF is closely coupled to

metabolic activity • Normal neural function depends on adequate matching between metabolic needs and blood supply • Cerebral blood flow is closely coupled to metabolic activity ‐ Regional differences in blood flow depending on neuronal activity e.g. -Increased blood flow to motor cortex when performing motor task - Decreased blood flow to areas not actively processing information

Stenosis:

narrowing of artery due to build up of plaque material => restricts blood flow

Thromboembolism:

piece of plaque broken off from a thrombus elsewhere in body (e.g. heart- A-fib is a risk factor) - travels through arterial system & lodges in brain artery, cutting off brain supply beyond this point

Both barriers help to....

protect the brain from exposure to toxic substances, hormones, foreign materials in the blood. Help to maintain environment of brain and nourish brain tissue. These fluids not only help to nourish the brain, but also help to remove metabolites and waste products that are then delivered to venous sinuses for removal. BBB regulates the composition of the interstitial fluid compartment. Blood CSF barrier regulates the composition of the CSF compartment (ventricles, cisterns, & subarachnoid space).

Superficial and deep sinuses converge at: and then?

the confluence of sinuses---> transverse sinuses----> sigmoid sinuses---> IJVs.

Thrombosis:

total blockage of an artery by a blood clot (thrombus), plaque or embolus.

Ependymal cell

type of neuronal support cell (neuroglia) that forms the epithelial lining of the ventricles (cavities) in the brain and the central canal of the spinal cord. Ependymal cells give rise to the epithelial layer that surrounds the choroid plexus (network of blood vessels in the walls of the lateral ventricles).

Aneurysm:

weakness of thin walled intima layer of artery that results in dilatation of artery lumen, prone to bursting when pressure builds up. Often occurs in circle of Willis.

What is the normal blood flow to the brain?

~750ml/min & remains constant throughout the day whether asleep, awake, standing up or lying down

Posterior circulation to the brain

• 20% of blood supply • Comprised of vertebral, basilar & posterior cerebral arteries

Anterior circulation to the brain

• 80% of blood supply • Derived from internal carotid arteries Major branches: ‐ Middle cerebral artery (MCA) ‐ Anterior cerebral artery (ACA)

Cerebrospinal fluid (CSF)

• A specialised extracellular fluid present in the cerebral cavity enclosing the brain and spinal cord ~140 mls Similar to plasma except is has low protein, no red cells, very few leukocytes & glucose at 60% of that of plasma ~500ml/day produced; most secreted by choroid plexuses in the lateral, 3rd and 4th ventricles

Mechanisms vary in different parts of stroke region. Infarct site vs. penumbra

• At infarct site, the core region, hypoxia is severe & brain tissue rapidly dies • Around the core is a rim of tissue, ischaemic penumbra, receiving some blood flow via collateral vessels. ‐ Brain cells undergo potentially reversible electrophysiological & metabolic failure, but have not yet entered signal cascades leading to cell death. ‐ Cells may remain viable for several hours until circulation can be restored, "salvageable tissue", thereby reducing the extent of functional deficit

Haemorrhagic stroke

• Blood vessel in or around brain bursts causing a bleed or haemorrhage within skull cavity • Long standing untreated hypertension a common cause • Intracranial arteries are thin‐walled and susceptible to rupture especially in untreated hypertension

Mechanisms of cell injury in ischaemic stroke

• Brain has high rate of oxidative metabolism => extremely vulnerable to hypoxic damage • Cell death: anoxia & loss of cell membrane integrity due to dysfunction of energy dependent ATPases • Pathophysiological effects of stroke involvecomplex sequence of events that evolve over space & time, that lead to cell death

Common effects of strokes in the brainstem may include problems with:

• Breathing & heart functions • Body temperature control • Balance & coordination • Weakness or paralysis • Chewing, swallowing, speaking • Vision • coma

Where does CSF circulate? How is it absorbed?

• CSF secreted by the ventricles circulates to the subarachnoid space that surrounds the brain and spinal cord • CSF is absorbed through arachnoidal villi that project into the dural venous sinuses of the brain. Arachnoid villi act like valves. If more CSF is generated, more is released into the sinuses.

Neurovascular coupling & functional imaging

• Changes in blood flow & oxygenation are coupled to underlying neuronal activity • Functional imaging reflects the metabolic demand of neural activity • Permits imaging of living brain and regions associated with specific mental processes

Cerebral pressure autoregulation - Classical view vs Emerging evidence in humans?

• Classical view: ‐ CBF autoregulated well between MAPs of 60‐140mmHg • Emerging evidence: ‐ CBF‐MAP relationship not as flat through a broad range of MAPs ‐ Cerebral autoregulation is more effective in protecting the brain from acute hypertension than hypotension What is apparent is that cerebral pressure is buffered more when MAP increases than when blood pressure drops. Cerebral regulation is more effective in protecting the brain for acute hypertension than hypotension.

Cerebral pressure autoregulation

• Daily activities cause marked fluctuations in arterial pressure • Cerebral blood flow is relatively "buffered" from these fluctuations in pressure ‐ known as cerebral pressure autoregulation Increase in MAP does not necessarily mean an increase in CBF. CBF is kept at a relatively constant blood flow over a wide pressure range. Autoregulation requires reflex adjustments in resistance of cerebral vasculature in response to changes in blood pressure. The cerebral vessels as well as the larger arteries in the neck supply the cerebral vasculature important in this.

Venous drainage of the brain

• Deep and superficial veins of the brain drain into dural venous sinuses

Increased CSF pressure in adults vs babies

• In adults, ↑CSF pressure compresses blood vessels (reduced O2 & nutrients) and damages brain tissue • In babies whose cranial sutures have not yet fused, ↑CSF pressure causes enlargement of the head and thinning of the cerebral hemispheres. • Fatal if untreated; in chronic cases can result in cognitive, motor & sensory impairment

Common effects of strokes in the cerebellum may include:

• Inability to walk & problems with coordination & balance (ataxia) • Dizziness • Headache • Nausea & vomiting • Strokes are less common in the cerebellum

Vertebral‐Basilar system

• Includes the two vertebral arteries, the basilar artery & their branches • Supplies the medulla, pons, midbrain, cerebellum & posterior regions of cerebrum (occipital & infero‐medial temporal lobes)

Sympathetic regulation of CBF:

• Innervation of entire cerebrovasculature • Disruption of sympathetic nerves causes minor increase in CBF => blood flow autoregulatory mechanisms override these small nervous effects • Important role in buffering surges in perfusion pressure e.g. during strenuous exercise - Constriction of large & intermediate‐sized brain arteries prevent transmission of high pressure to small brain blood vessels, protecting them from damage

Cholinergic regulation of CBF:

• Innervation of intracranial vessels proximal to Virchow‐Robin spaces • Limited data available for functional role, minor?

The major blood supply to the brain is via 2 pairs of arteries:

• Internal carotid arteries • Vertebral arteries ( VA's fuse together near the junction of the pons & medulla to form the basilar artery)

Cerebrum: Effects of a right hemisphere stroke may include:

• Left‐sided weakness (left hemiparesis) or paralysis (left hemiplegia) & sensory impairment • Denial of paralysis or insight into problems created by stroke ("left neglect") • Visual problems including inability to see left visual field of each eye • Spatial problems with depth perception or directions (e.g. up, down, front or back) • Inability to localise or recognise body parts • Inability to understand maps, find objects (e.g. clothing, toiletries) • Memory problems • Behavioural problems e.g. depression, impulsivity, lack of concern about situations, inappropriateness

Effects of strokes in the spinal cord may include:

• Paraparesis or quadriparesis (corticospinal tracts) • Loss of bladder & bowel control, loss of pain & temperature sensation below the lesion (spinothalamic tracts) • (Proprioception & discriminative touch (dorsal columns) are spared) • If cervical or lumbar spinal cord is involved atrophic weakness of upper or lower extremity muscles (anterior/ventral horns) can occur Brachial plexus= C5- T1. Lumbar plexus= L1-L4. • Penetrating arteries of the anterior spinal artery enter the right and left halves of spinal cord. If one side suffers a stroke, there is: - ipsilateral weakness - contralateral loss of pain and temperature sensation ^Depends on which area of SC is effected and on whether one or both of the circulations are effected.

Endothelium regulation of CBF:

• Potent regulator of CBF • Nitric oxide (NO), endothelium‐derived hyperpolarization (EDH), prostanoids (PGs ,TXs. PCs)→vasodilation • Pathological conditions, **endothelin (vasoconstriction) → ischemia & vasospasm

Cerebrum: Effects of a left hemisphere stroke may include:

• Right‐sided weakness (right hemiparesis) or paralysis (right hemiplegia) & sensory impairment • Problems with speech & understanding language (aphasia) • Visual problems including inability to see right visual field of each eye • Impaired ability to do calculations or to organise, reason & analyse items • Behavioural changes e.g. depression, hesitancy, cautiousness • Impaired ability to read, write & learn new information • Problems with memory

Neurovascular coupling

• Spatiotemporal coupling between brain activity & CBF • Mediated by neurovascular unit: functional network of neurons, glia & microvasculature of the brain Pial arteries send off branches that penetrate the material of the brain tissue. Development of close association of astrocytes, neurons, and underlying cerebral blood vessels.

Stroke / cerebrovascular accident

• Stroke is the 2nd leading killer of Australians after coronary heart disease • Characterised by temporary, or permanent, loss of function of brain tissue caused by interruption of blood supply • Strokes: - 75% due to infarction (neuronal death when ischemia is severe and prolonged) - 25% subarachnoid or intracerebral haemorrhage FAST acronym applies for MCA stroke. Less difficult to pick up sx in people w/ stroke affecting emotional areas.

Transient ischaemic attacks

• Temporary loss of brain function (~< 30 min) • Total recovery within 24 hrs • Commonly caused by emboli that break off atherosclerotic plaques • Can be caused by spasm of a cerebral artery (e.g. increased endothelin release from endothelium) • Symptoms mimic those of true strokes • Early warning of a future stroke (20% of patients go on to have a full stroke)

Metabolic regulation of cerebral blood flow

• The cerebrovasculature is exquisitely sensitive to CO2 • Increases in CO2 evoke vasodilation • CO2+H20 → carbonic acid → H+ • CO2 & H+ is formed during metabolic activities • The hyperaemia (excess of blood in vessels) serves to flush these neurologically damaging agents from the brain tissue • Hypocapnia increases cerebrovascular resistance => ↓CBF Accumulation of H+ in the ECF around cerebral blood vessels is what prompts vasodilation. Increases in H+ ion concentration decreases neuronal activity.

Brain is divided into 3 main regions: Cerebrum, Cerebellum, brain stem Strokes in these regions can have very different effects. Cerebrum stroke:

• controls movement, sensation, speech, thinking, reasoning, memory, vision, regulation of emotions Stroke may impair: movement & sensation speech & language, eating & swallowing vision cognitive ability perception & orientation to surroundings self care ability bowel & bladder control sexual ability

Smoking risk factor

↑ BP, damages arterial walls