Transcript Glial Cells
Neuronal Microenvironment Block 3 2012 • Reading Assignment: Textbook of Medical Physiology, 12th edition, Guyton & Hall • Chapter 61, pp. 743-752 BECF & CSF • Neuronal microenvironment includes the extracellular fluid (ECF), capillaries, glial cells, and adjacent neurons • The concentration of solutes in brain ECF (BECF) fluctuate with neural activity. Similarly, changes in BECF can influence nerve cell behavior – Blood-brain-barrier (BBB) protects BECF from fluctuations in blood composition – The cerebrospinal fluid (CSF) strongly influences the BECF composition – The surrounding glial cells “condition” the BECF Cerebrospinal Fluid CSF is a colorless, watery liquid which fills the ventricles of the brain and forms a thin layer around the outside of the brain and spinal cord in the subarachnoid space CSF is secreted by a highly vascularized epithelial structure, choroid plexus The ventricles of the brain are four small compartments Each contains a choroid plexus and is filled with CSF Ventricles and Subarachnoid Space The two lateral ventricles are the largest and each communicate with the third ventricle via the two interventricular foramina of Monro The third ventricle communicates with the fourth ventricle by the cerebral aqueduct of Sylvius The fourth ventricle is continuous with the central canal of the spinal cord CSF escapes from the fourth ventricle and flows into the subarachnoid space via three foramina Two laterally placed foramina of Luschka Midline opening in the roof of the fourth ventricle, foramen of Magendie The Brain Ventricles & The CSF Blumenfeld, Neuroanatomy VENTRICULAR SYSTEM Blumenfeld 131 Blumenfeld, Neuroanatomy VENTRICULAR SYSTEM The Cerebrospinal Fluid Circulation Blumenfeld, Neuroanatomy The Meninges The brain and spinal cord are covered by three membranes: The innermost layer is pia mater The middle is arachnoid mater (membrane) * between the arachnoid mater and pia mater is the subarachnoid space (filled with CSF) The outermost layer is dura mater Blumenfeld, Neuroanatomy Pia mater • The pia mater is a thin layer of connective tissue cells • Very closely applied to the surface of the brain and covers blood vessels • The glia limitans adjoins the pia from the brain side and is separated from the pia by a basement membrane – Pia adheres associated glia limitans very tightly; this combined structure called the pial-glial membrane Arachnoid Membrane & Dura Mater The cells of the arachnoid membrane are linked together by tight junctions The arachnoid isolates the CSF in the subarachnoid space from blood in the overlying vessels of the dura mater The dura mater is a thick, inelastic membrane that forms an outer protective envelope around the brain The dura has two layers that split to form the intracranial venous sinuses The Meninges & Ependymal Cells Arachnoid granulations Choroid Plexuses Secrete CSF Most of the CSF is produced by the choroid plexuses which are located in ventricles Capillaries also form a small amount of CSF CSF production is 500 ml/day and CSF volume of 150 ml is replaced three times a day CSF percolates throughout the subarachnoid space, then absorbed into venous blood from the superior sagittal sinus Secretion of CSF Choroid epithelial cells are bound to one another by tight junctions, which makes the epithelium an effective barrier to free diffusion Ion concentration of CSF is rigidly maintained Micronutrients are selectively transported Composition of Cerebrospinal Fluid SOLUTE PLASMA (mM OF PROTEINREE PLASMA) CSF (mM) CSF/PLASMA RATIO Na+ 153 147 0.96 K+ 4.7 2.9 0.62 Ca2+ 1.3 (ionized) 1.1 (ionized) 0.85 Mg2+ 0.6 (ionized) 1.1 (ionized) 1.8 110 113 1.03 24 22 0.92 0.75 (ionized) 0.9 1.2 7.40 7.33 2.6 0.7 0.27 7 g/dl 0.03 g/dl 0.004 290 290 1.00 Cl- PH Aminoacids acids Amino Proteins Osmolality (mOsm) Absorption of CSF the sites of absorption are specialized evaginations of the arachnoid membrane into the venous sinus “arachnoid granulations/villi” “One-way valves” Hydrocephalus Hydrocephalus – excessive CSF in cranial cavity 1) Communicating Hydrocephalus – impairment of reabsorption in arachnoid villi or of flow in subarachnoid space 2) Noncommunicating (obstructive) hydrocephalus – obstructions of flow within ventricular system “Normal-Pressure” Hydrocephalus • Spinal tap reveals normal pressure readings, but MRI of the head will show enlargement of all four ventricles – An infection or inflammation of the meninges damages arachnoid villi, and causes impaired CSF absorption • Patients typically have progressive dementia, urinary incontinence, and gait disturbance • CSF shunt to venous blood or to the peritoneal cavity helps reducing CSF pressure Lumbar Puncture • Procedure to collect CSF from subarachnoid space is called lumbar puncture • The spinal cord ends as a gradual taper, known as the conus medullaris, typically coming to an end at the lower border of L1 or at the upper border of L2. – The nerve roots of the cauda equina “sprout” from the conus medullaris and extend caudally within the vertebral canal as far as the caudal end of the sacrum. • Spinal nerves exit the vertebral canal inferior to their named vertebrae, except for cervical spinal nerves, which exit through the intervertebral foramina superior to their named vertebrae Lumbar Puncture Blumenfeld, Neuroanatomy The Extracellular Space The average width of the space between brain cells is 20 nm Glial cells express neurotransmitter receptors, and neurons have extrajunctional receptors >>> capable of receiving messages sent via BECF – Numerous trophic molecules secreted by brain cells diffuse in the BECF to their target cells Leaky regions of the BBB Blood-Brain Barrier CNS blood vessels exclude certain substances from brain tissue : “blood-brain barrier” Brain needs to be protected from the constituent variations of blood Neurons within the circumventricular organs are directly exposed to blood solutes and macromolecules Part of neuroendocrine control system for maintaining osmolality, appropriate hormone levels etc. Humoral signals are integrated by connections of circumventricular organ neurons to endocrine, autonomic, and behavioral centers within the CNS The BBB function of brain capillaries Brain capillary endothelial cells are fused to each other by tight junctions – The tight junctions prevent water-soluble ions and molecules from passing from the blood into the brain via paracellular route – Electrical resistance of the cerebral capillaries is 100 to 200 times higher than other systemic capillaries Glial Cells The three major types of glial cells in the CNS are astrocytes, oligodendrocytes, and microglial cells Glial cells are about 10-fold more numerous than neurons, and they can proliferate throughout life Glial Types GLIAL CELL TYPE SYSTEM LOCATION GFAP Fibrous CNS White matter Positive Protoplasmic CNS Gray matter Weakly positive Radial glial cells CNS Throughout brain during development Positive Müller cells CNS Retina Positive Bergmann glia CNS Cerebellum Positive Ependymal cells CNS Ventricular lining Positive Oligodendrocytes CNS Mainly white matter Negative Microglial cells CNS Throughout the brain Negative Satellite cells PNS Sensory and autonomic ganglia Weakly positive Schwann cells PNS Peripheral axons Negative Enteric glial cells ENS Gut wall Positive Astrocytes Astrocytes • Astrocytes modifies and controls the immediate environment of neurons – Fibrous astrocytes have long, thin and well defined processes – Protoplasmic astrocytes have shorter, frilly processes • The cytoskeleton of all the astrocytes composed of a unique protein “glial fibrillar acidic protein” • During development, radial glial cells are present: – create an organized scaffolding by spanning the developing forebrain from the ventricle to the pial surface • Müller cells are retinal astrocytes • Bergmann glial cells are located in the cerebellum Astrocytes • Astrocytes contain all the glycogen present in the brain – also contain all the enzymes needed for metabolizing glycogen • The brain’s glucose needs is supplied by blood, in the absence of glucose from blood, astrocytic glycogen could sustain the brain for about 5 minutes Astrocytes break glycogen down to glucose and even further to lactate, which is aerobically metabolized by nearby neurons >>> substrate buffering Role of Müller Cells in Spatial Buffering Astrocytes Synthesize Neurotransmitters Astrocytes synthesize at least 20 neuroactive compounds, including glutamate and GABA Glutamate precursor glutamine is manufactured only in astrocytes, by astrocyte-specific enzyme glutamine synthetase Glutamine is released by astrocytes to the BECF to be taken up by neurons Role of Astrocytes in the glutamateglutamine cycle Glutamine is also important for the GABA synthesis Neuronal glutamic acid decarboxylase converts glutamine to GABA After its use as neurotransmitter by neurons, some of glutamate is taken up into astrocytes via high-affinity uptake systems This system maintain extracellular glutamate concentration around 1uM If transmembrane ion gradients break down under pathologic conditions, high-affinity uptake systems may work in reverse • Excessive accumulation of glutamate in the BECF –induced by ischemia, anoxia, hypogylcemia, or trauma- can lead to neural injury • In anoxia and ischemia, the sharp drop in cellular ATP levels inhibits the Na-K pump and leads to large increases in [K+]o and [Na+]i – These changes result in membrane depolarization along with a burst of glutamate release from vesicles • The inability of astrocytes to remove glutamate from the BECF under these pathologic conditions makes extracellular glutamate levels too high to become toxic for neurons Oligodendrocytes • The primary function of oligodendrocytes in the CNS is to provide and maintain myelin sheaths on axons – Myelin is the insulating electrical tape of the nervous system • Oligodendrocytes in white matter has 15 to 30 processes, each connecting a myelin sheath to the oligodendrocyte’s cell body – Each myelin sheath wraps many times around the long axis of one axon Myelin The constituent proteins in PNS and CNS myelins are somewhat different In the Peripheral nervous system, a single Schwann cell provides a single myelin segment to a single axon of a myelinated nerve Ensheathed versus myelinated axons Oligodendrocytes • Oligodendrocytes and myelin contain most of the enzyme carbonic anhydrase in the brain – Carbonic anhydrase is important in CO2/HCO3- buffer system • pH imbalance in the brain reduces seizure threshold • Oligodendrocytes are also involved with iron metabolism Microglial Cells • Microglial cells derive from cells related to the monocyte/macrophage lineage – Microglia represent 20% of the total glial cells within CNS • These cells are rapidly activated by injury to the brain, proliferate and become phagocytic • Microglia are also the most effective antigen-presenting cells within the brain