Neuro: Meninges, Vessels, & CSF

MENINGES Meninges are connective tissue coverings around neural tissue in the CNS. The meninges in the CNS are continuous with the connective tissue sheaths around nerves in the PNS. The spaces between the meninges are unique to the CNS. CNS Epidural Space: This is only a potential space between the dura and bone. This space should NOT exist in healthy people. Vessels: Contains the middle meningeal artery. Dura Mater: Tightly adherent to overlying bone but loosely adherent to underlying arachnoid mater. Tightly sealed from the arachnoid mater to prevent CSF leakage into the cranial vault. Subdural Space: This is only a potential space between the dura and arachnoid maters. This space should NOT exist in healthy people. Vessels: Contains the bridging veins. Arachnoid Mater: Loosely adherent to the underlying pia mater. Loosely sealed from the pia mater to allow CSF to pass into the brain cortical tissue. Subarachnoid Space: This is a real space in healthy people. Ends at S2. CSF: Found in the subarachnoid space ONLY. Arachnoid Granulations: Reabsorb the circulating CSF. Vessels: Large vessels traverse this space. Arachnoid Trabeculae: Web-like threads of CT run through this space to bridge the arachnoid and pia maters. Pia Mater: Very porous to allow CSF to cross. Vessels: The pia mater is extremely vascular. It dives down to follow the gyri and sulci, bringing its vessels with it. PNS

Epineurium (Outer): Around entire nerve.

Perineurium (Middle): Around fascicle. Acts as a permeability barrier.

Endoneurium (Inner): Around myelin sheath of individual neurons.

DURAL FOLDS Falx Cerebri: Separates the left and right cerebral hemispheres. Attaches to the crista galli of the ethmoid anteriorly and the tentorium cerebeli posteriorly. Falx Cerebelli: Small triangle of dura matter with its base attached to the tentorium cereblli and its posterior margin to the occipital bone. Tentorium Cerebelli: A double fold of dura mater that separates the cerebellum (inferior) from the cerebrum (superior). This fold is sharp enough to cut through the brain tissue during cerebral edema.

VENTRICULAR SYSTEM & CEREBRAL SPINAL FLUID CEREBRAL SPINAL FLUID (CSF) Location: Subarchnoid space of brain + central canal of spinal cord. Production: 500 ml/day. Turns over 4 times/day, since brain can only hold 125 ml. Made by ependymal cells of the choroid plexus (50-70%), around blood vessels, along ventricular walls. Ependymal cell transporters move Na, Cl, CO3 across the BBB from systemic capillaries into the ventricles (uses ATP). Drainage: Returns to systemic venous circulation via arachnoid granulations of the superior sagittal sinus. Functions: 1) Protection; 2) Transport Nutrients; 3) Remove Wastes & NTs; 4) Maintain CNS Environment. Normal Pressure: 70-180 mm H2O. Normal Color: Clear and thin. Normal Composition Compared to Plasma Glucose Lower (60%) Protein Lower (1%) Immunoglobulin Lower (0.2-0.4%) Cells None K & Ca Lower Na, Cl, HCO3 Same Mg Higher VENTRICULAR SYSTEM Ventricles: 1) 2 Lateral Ventricles (Anterior Horn, Body, Trigone, Posterior Horn); 2) Third Ventricle; 3) Fourth Ventricle. The third and fourth ventricles are connected by the Cerebral Aquaduct. The fourth ventricle continues to the central canal of the spinal cord. Apertures: The fourth ventricle has 3 openings: 2 foramen of Luschka (lateral) and 1 foramen of Monroe (medial). Choroid Plexus: Comprised of ependymal cells. Located on the roof of the third & fourth ventricles, the recesses of the third ventricle, and the body & inferior horn of the lateral ventricles. Cisterna Magna: Large CSF collection between the cerebellum and medulla. Cisternal puncture can be used as an alternative to lumbar puncture. FLOW OF CSF Major Path: Choroid Plexus of Lateral Ventricles Lateral Third Cerebral Aquaduct Fourth Apertures Subarachnoid Space Arachnoid Granulations Superior Sagittal Sinus Confluence of Sinuses Transverse Sinus Sigmoid Sinus Internal Jugular Vein Systemic Circulation Minor Path: Choroid Plexus of Fourth Ventricle Central Canal of Spinal Cord Subarachnoid Space

VEINS & VENOUS SINUSES Cerebral veins venous sinuses confluence of sinuses transverse sinus sigmoid sinus internal jugular vein CEREBRAL VEINS Follow the cerebral arteries. VENOUS SINUSES: Run INSIDE the dura mater between its periosteal (bone) and meningeal layers to drain the cerebral capillary beds. Superior Sagittal Sinus: Site of CSF reabsorption via arachnoid granulations. Cavernous Sinus: A collection of venous sinuses on either side of the pituitary. Receives deox blood from the sup and inf ophthalmic veins, sphenoparietal sinus, and middle cerebral vein. Carries deox blood to the internal jugular vein. o The ophthalmic veins receive blood from the facial vein. Neither have valves to prevent retrograde flow. Thus, infections from their vascular territories (the danger area of the face) can easily spread to the brain (facial v ophthalmic v cavernous sinus). o A number of important structures pass through the cavernous sinus: Nerves: CN3, 4, 6 (extraocular muscles) and CN5-1, -2 (face sensation). Vessels: Internal carotid artery. This is the only instance in the body of

an artery passing through a vein. Cavernous Sinus Syndrome: Opthalmoplegia, ophthalmic & maxillary facial
sensory loss.

INTERNAL JUGULAR VEIN Exits the cranial cavity via the internal jugular foramen.

IMMUNITY IN THE CNS Nervous system infections are rare and life-threatening complications of SYSTEMIC infections. There is a blood-brain barrier but no brain-CSF barrier. o Pathogens and immune cells cannot easily cross from the blood to the brain. o Pathogens can easily cross from the CSF to the brain. o Once in the brain, pathogens CANNOT easily spread because neural tissue is extremely dense (the space between neurons is less than the size of a viral particle). o Once inside a neuron, pathogens CAN easily spread via axons to other distant neurons.

BLOOD BRAIN BARRIER (BBB) Location: Throughout the CNS. Components 1. Capillary endothelial cells : These are continuous with tight junctions. 2. Basement membrane 3. Astrocyte foot processes (glia limitans): Completely encircle the endothelial cells to help maintain their tight junctions. Unlike all other organs, the brain has virtually no connective tissue. Other organs have their vessels embedded in stroma, but the brains vessels are supported ONLY by astrocytes and suspended in CSF. This is what makes the brain so soft. Function o To closely regulate the entry and export of materials to and from the CNS. o Hydrophobic molecules (lipids) cross rapidly via diffusion. o Hydrophilic molecules (glucose, amino acids) cross slowly via carrier-mediated transport. o Hypothalamic inputs and outputs permeate the BBB in order to dump hormones produced by the brain into the blood. Circumventricular Organs: Specialized areas of the brain exposed directly to blood. This allows blood-borne substances to affect brain function, and the brain to adjust blood chemistry. Located near the third or fourth ventricles. o Area Postrema: Vomiting in response to toxemia. o OVLT: Osmotic sensing. o Neurohypophysis (Posterior Pituitary): ADH release. o Pineal Gland: Melatonin release. o Median Eminence: Regulates the adenohypophysis (anterior pituitary). IMMUNE FUNCTION WITHIN THE CNS The CNS is isolated from the immune system by the BBB. The CNS has no lymphatic system (lymphatic function is NOT replaced by CSF). The CNS has no innate immunity (no complement and few phagocytosing microglia). The CNS has very limited humoral immunity (small amount of IgG, IgA, IgM). It is very difficult for pathogens to enter the CNS. Systemic titers must be extremely high in order to breed just a few genetic variants that can cross the BBB. However, once pathogens are inside the CNS, it is very difficult to eradicate them because the CNS has limited immunity. o This is why mild systemic infections are life-threatening once they spread to the brain. o If the infection spreads through a break in the BBB, immune mediators in the serum will also cross. These mediators will mount an inflammatory reaction in the brain.

Acute Bacterial CNS Infection: Complement & PMNs cross the BBB first. Chronic Bacterial or Viral CNS Infection: Mononuclear cells (T-cells, monocytes) cross the BBB first.

PERFUSION IN THE CNS

CEREBRAL BLOOD FLOW (CBF): The brain consumes 15% of CO. Hyperperfusion (Hyperemia) o Cause: Hypoxia, hypercapnia, and general anesthesia. o Effect: High CBF increases ICP. Hypoperfusion (Ischemia) o Cause: Increased ICP. Results in ischemic brain disease. High ICP decreases CBF by 1) compressing cerebral arteries and raising CVR; and 2) increasing interstitial hydrostatic pressure, which prevents filtration of nutrients from capillaries into the brain parenchyma. CEREBRAL PERFUSION PRESSURE (CPP): Must be maintained within a very narrow range because Low CPP (Vasoconstriction) o Effect: Directly decreases CBF and oxygen delivery. o Compensation (Vasodilatory Cascade): Cerebral arteries will compensate for low CPP by vasodilating, which restores CPP at the expense of raising ICP. If ICP becomes too high, it will compress the cerebral arteries, which decreases CBF and oxygen delivery. Compensatory vasodilation can thus be counterproductive. High CPP (Vasodilation) o Effect: Indirectly decreases CBF and oxygen delivery by raising ICP. o Compensation (Vasoconstrictive Cascade): Cerebral arteries will compensate for high CPP by vasoconstricting.

Cerebral Blood Flow = Cerebral Perfusion Pressure/Cerebral Vascular Resistance (CBF = CPP/CVR) Analogous to Perfusion = Mean Arterial Pressure/Total Peripheral Resistance (Q = MAP/TPR) Cerebral Perfusion Pressure = Mean Arterial Pressure Intracranial Pressure (CPP = MAP ICP) Unless Jugular Venous Pressure (JVP) > ICP. Then CPP = MAP JVP.

REGULATION OF PERFUSION Autoregulation: Cerebral arteries have an intrinsic ability to maintain CBF at the expense of CVR. This mechanism is effective between 50 < MAP < 150, but fails outside this range. o When MAP Rises: Cerebral arteries constrict (increase CPP) to prevent CBF from also rising. o When MAP Falls: Cerebral arteries dilate (decrease CPP) to prevent CBF from also falling. When PCO2 Rises (PCO2 Drive): Cerebral arteries dilate (decrease CPP) to increase CBF and O2 delivery. o This is the primary physiological drive under normal non-hypoxic conditions (PO2 > 50 mmHg). When PCO2 Falls (Acute Hypocapnic Vasoconstriction): If the PCO2 drive causes cerebral arteries to dilate (increase CPP, CBF, and ICP) when PCO2 rises, then they will constrict (decrease CPP, CBF, and ICP) when PCO2 falls. You can thus RELIEVE high ICP in acute cerebral edema (stroke, trauma) by INDUCING HYPERVENTILATION. This effect only lasts 5 hours, after which the CBF begins to return to homeostasis. When PO2 Falls (PO2 Drive): Cerebral arteries dilate (decrease CPP) to increase CBF and O2 delivery. o This drive only becomes active under life-threatening hypoxic conditions (PO2 < 50 mmHg).

ARTERIES OF THE CNS ANTERIOR CIRCULATION (Internal Carotid) Supplying Cerebrum o Anterior Cerebral Artery (ACA) o Middle Cerebral Artery (MCA)

CIRCLE OF WILLIS: Connects ant and post circulations. Providing Anastamoses o Anterior Communicating Artery (AComm): Anastamoses the R ACA and L ACA. o Posterior Communicating Artery (PComm): Anastamoses the R PCA & R MCA (and the L). POSTERIOR CIRCULATION (Subclavian) Supplying Cerebrum o Posterior Cerebral Artery (PCA): Perforating branches (medial thalamus, third ventricle), Choroidal Branches (third ventricle, choroid plexus, cerebral peduncle, fornix, thalamus, caudate), Cortical Branches (temporal lobe, medial occipital lobe). Occlusion: Contralateral loss of STT, contralateral hemianopia with macular sparing, prosopagnosia, Webers Syndrome, contralateral CN7, CN9 & CN10 deficits, ipsilateral CN3 deficit with Horners Syndrome. Supplying Cerebellum o Posterior Inferior Cerebellar Artery (PICA): Medial & Lateral Branches (cerebellum, choroid plexus, fourth ventricle). Occlusion: Wallenberg (Lateral Medullary) Syndrome o Anterior Inferior Cerebellar Artery (AICA): Labryinthine Artery (inner ear; is sometimes a branch of the basilar artery instead of the AICA). Supplying Spine o Basilar Artery: Confluence of the two bilateral vertebral arteries. o Vertebral Artery: One of the branches of the subclavian artery (vertebral, internal mammary, thyrocervical, costocervical, dorsal scapular). o Anterior Spinal Artery: Arises from vertebral artery to supply anterior spinal cord. Occlusion at Spinal Cord: Anterior Spinal Artery Syndrome Bilateral loss of CST and STT. Occlusion at Medulla: Medial Medullary Syndrome. WATERSHED AREAS: Where two circulations (ant or post) meet. Vulnerable to ischemia. Damage causes proximal limb weakness and defects in visual processing. 1. Between ACA and MCA territories. 2. Between PCA and MCA territories.

Blood Supply

Artery Posterior spinal

Region Spinal cord

Posterior spinal Vertebral artery Vertebral artery Anterior spinal

Medulla (closed) Medulla (closed) Medulla (open) Spinal cord

Specific nucleus/tract Dorsal column Fasciculus gracilis Fasciculus cuneatus Dorsal horn Nucleus gracilis Nucleus cuneatus Trigeminal nucleus Inferior olivary nucleus Reticular formation Corticospinal tract Intermediate zone Anterior horn Spinothalamic tract Pyramidal tract Pyramidal tract Medial lemniscus Tectospinal tract Medial longitudinal Fasciculus Dorsal longitudinal Fasciculus Hypoglossal nucleus Solitary tract Inferior cerebellar Peduncle Spinal trigeminal tract Rubrospinal tract Fibers of vagus nerve Anterolateral system Accessory cuneate Nucleus Vestibular nuclei Facial nerve Tectospinal tract Spinal trigeminal tract Medial longitudinal Fasciculus Reticular formation Medial lemniscus Corticospinal tract Corticobulbar tract Pontine nuclei

Symptoms

Anterior spinal Anterior spinal

Medulla (closed) Medulla (open)

Posterior inferior Cerebellar artery

Medulla (open)

Anterior inferior Cerebellar artery and Basilar artery Long circumferential branches

Pons

Pons Basilar artery Paramedian branches

Basilar artery Short circumferential Superior cerebellar Artery

Pontocerebellar fibers Pons Cerebellar peduncles Deep cerebellar nuclei Interposed nuclei

Posterior cerebral artery Thalamus Red nucleus Subthalamic nucleus Motor and sensory strip Anterior cerebral (leg areas) Artery Middle cerebral Penetrating branches Middle cerebral artery Globus pallidus Caudate Broca's area Wernicke's area Auditory area Motor and sensory strip (all except leg areas) Visual area Hippocampus

Posterior cerebral Artery

Blood Supply of CNS Brain Division Spinal cord Medulla Pons Cerebellum Midbrain Diencephalon Thalamus Hypothalamus Subthalamus Basal ganglia Globus pallidus Striatum Cerebral cortex Frontal lobe Parietal lobe Occipital lobe Temporal lobe Major Artery Anterior spinal, posterior spinal, radicular arteries Vertebral arteries Basilar Vertebral, basilar Basilar, posterior cerebral, anterior choroidal, Posterior choroidal Posterior communicating, posterior choroidal, Posterior cerebral Anterior cerebral, posterior communicating, Posterior cerebral Anterior choroidal, posterior choroidal, Posterior communicating, posterior cerebral Anterior choroidal Middle cerebral Anterior cerebral Anterior cerebral, middle cerebral Posterior cerebral, middle cerebral Middle cerebral, posterior cerebral,

Posterior choroidal Internal capsule Anterior limb Genu Posterior limb Retrolenticular Anterior cerebral, middle cerebral Middle cerebral Middle cerebral, anterior choroidal Anterior choroidal