Midterm 1

• Pain sensitivity within the skull is restricted to the intracranial meninges (headache)
• Three layers of the meninges cover the brain and spinal cord:

  • Outer thick layer is the dura mater
  • Periosteal layer attached to the inner surface of the skull
  • Meningeal layer covering the brain
  • Middle, impermeable layer is the arachnoid mater, adjoins dura, separated from Pia by subarachnoid space filled with CSF
  • Pia mater is delicate, permeable, innermost, resting on the brain surface
• Arrangement of periosteal and meningeal layers:

  • Both layers are closely united except at the venous sinuses
  • Periosteal layer continuous with periosteum on the outside of skull bones and cranial sutures
  • Meningeal layer penetrates spaces in cerebral hemispheres
• Two important partitions arise from the meningeal layer:

  • Falx cerebri: sickle-shaped fold separating the cerebral hemispheres, forms the floor of the superior sagittal sinus
  • Tentorium cerebelli: separates the posterior cranial fossa from the rest of the cranial vault, arches upward along the median line to become continuous with falx cerebri
• Epidural space and hemorrhage/hematoma:

  • Location: tight potential space between the dura and the skull
  • Usual cause: rupture of the middle meningeal artery during head trauma
  • Symptoms: initially no symptoms (lucid interval), then hematoma compresses the brain, increased ICP, herniation, and potential death unless surgery
• Subdural space hemorrhage/hematoma:

  • Location: potential space between the dura and the loosely adherent arachnoid
  • Usual cause: rupture of the bridging veins passing through en route to dural sinuses
  • Types: acute (high-velocity impact) and chronic (seen in the elderly with brain atrophy)
• Arachnoid mater, subarachnoid space, and Pia mater:

  • Arachnoid mater separated from Pia by subarachnoid space
  • Arachnoid connected to Pia by delicate threads (trabeculae)
  • Arachnoid granulations: site where CSF diffuses into the venous sinuses
  • Pia mater: vascular membrane adhering closely to the brain, arteries carry sheath of Pia as they enter the parenchyma
• Headaches:

  • Brain has no pain receptors, pain comes from trigeminal and first three cervical nerves innervating the meninges and vasculature
  • Dura above tentorium innervated by trigeminal ganglion
  • Dura below tentorium innervated by cervical nerves (1-3)
  • Migraine headache depends on the activation of trigeminal afferents that densely innervate the meninges
• Innervation of the intracranial dura mater:

  • Pain fibers are activated due to changes in vessel size during migraines
• Clinical conditions related to meninges:

  • Meningitis: inflammation of meninges
  • Meningiomas: tumors in meninges
  • Space-occupying lesions: increase ICP and stretching of dura
  • Cluster headache: lancinating or boring periorbital pain
  • Hangover: toxic effect on meninges
• Coupling mechanisms for blood flow changes:

  • Direct action of neuronally derived substances like glutamate and nitric oxide on the vasculature
  • Cellular mediators of neurovascular coupling include astrocytes, interneurons, and pericytes
  • Afferents from the basal forebrain modulate regional blood flow via acetylcholine release
  • Vasoactive substances released by cortical interneurons such as VIP and NO
  • Interneurons may fine-tune local hemodynamics, with astrocytes or pericytes possibly acting as intermediates
• Candidate neurovascular coupling pathways:

  • Astrocytes sense glutamate via metabotropic glutamate receptors and increase intracellular calcium, leading to the generation of arachidonic acid and prostaglandins
  • Endothelial cells increase intracellular calcium through TRP cation channels and IP3-mediated release from intracellular stores
  • Endothelial receptor targets include acetylcholine, bradykinin, adenosine diphosphate, ATP, uridine triphosphate, and adenosine
  • Endothelial hyperpolarization through calcium-dependent potassium channels can lead to SMC relaxation
• • Pericytes possess SMC-like properties and can relax in response to NO and PGI2 from astrocytes, neurons, or endothelial cells
• Retrograde propagation of vasodilation:

  • Rapidly propagated retrograde vasodilation mechanism during functional hyperemia mediated via endothelial hyperpolarization
  • EDHF-type propagated vasodilation explains rapid dilation of distant pial arteries
  • Endothelial signaling may be initiated at the capillary level and travel retrograde along an integrative vascular route
• Ventricular system:

  • Relationships between intracranial fluid compartments and the blood-brain and blood-cerebrospinal fluid barriers
  • Interstitial fluid in the brain and cerebrospinal fluid in the intraventricular and subarachnoid spaces are separately compartmentalized
  • Homeostasis of fluid compartments is regulated by the blood-brain and blood-CSF barriers
• Cerebrospinal fluid secretion and circulation:

  • Choroid plexus secretes CSF through specialized capillary networks
  • CSF production involves ultrafiltration of plasma and net secretion of NaCl and NaHCO3
  • CSF circulates through ventricles and subarachnoid space, absorbed by dural venous sinuses through arachnoid granulations
• Elevated intracranial pressure:

  • Increase in brain tissue, blood, or CSF volume leads to increased ICP
  • Severely elevated ICP can cause decreased cerebral blood flow and brain ischemia
  • Symptoms include headache, altered mental status, nausea, papilledema, visual loss, and Cushing’s triad
• Lumbar puncture (spinal tap):

  • Needle inserted between fourth and fifth lumbar vertebrae into lumbar subarachnoid space
  • Normal intracranial pressure ranges from 65 to 195mm CSF or 5-15mmHg
  • Used to diagnose conditions like papilledema
• Papilledema:

  • Optic disc swelling due to increased intracranial pressure
  • Pressure on optic nerve head forces it inward, obstructing axonal transport and venous return
• Hydrocephalus:

  • Condition caused by excess CSF in intracranial cavity
  • Can result from excess production, obstruction of flow, or decreased reabsorption
  • Divided into communicating and noncommunicating types based on flow obstruction
• Hydrocephalus can be classified into communicating and noncommunicating types
• Communicating hydrocephalus is caused by impaired CSF absorption
• Noncommunicating hydrocephalus is caused by obstruction of flow within the ventricular system
• Main symptoms and signs of hydrocephalus include headache, nausea, vomiting, cognitive impairment, decreased level of consciousness, papilledema, and decreased vision
• Treatment for hydrocephalus usually involves a procedure that allows CSF to bypass the obstruction and drain from the ventricles
• An external ventricular drain (ventriculostomy) can be used to drain fluid from the lateral ventricles into a bag outside of the head
• A more permanent treatment is a ventriculoperitoneal shunt, where the shunt tubing drains into the peritoneal cavity of the abdomen
• Barriers in the central nervous system are present at three main sites
• The brain endothelium forms the blood-brain barrier
• The arachnoid epithelium forms the middle layer of the meninges
• The choroid plexus epithelium secretes CSF
• The blood-brain barrier is essential for maintaining a constant internal environment
• Endothelial cell tight junctions prevent water-soluble ions and molecules from passing from blood into the brain
• Astrocytic endfeet provide a continuous covering of the capillaries and facilitate substance transport
• Tight junctions in the blood-brain barrier are composed of claudins, occludins, and junctional adhesion molecules
• Olfactory system organization involves peripheral and central components
• Olfactory receptor neurons in the olfactory epithelium interact with the olfactory bulb in the central nervous system
• Odorant perception in mammals is influenced by factors like the number of olfactory receptor neurons and odorant receptor proteins
• Humans can detect different odors at specific concentrations, with some odors perceived differently at varying concentrations
• Anosmia is the loss of the ability to detect odors and can be caused by various factors including aging, trauma, and neurodegenerative conditions