CPAT3201 - Lectures 5-6

What are the unique features of the CNS that affect injury and repair?

enclosed in bony skull, surrounded by CSF, has meninges, is a closed system with BBB and blood-CSF barriers, high metabolic demand (20% O2 use), post-mitotic neurons with limited repair, and functional specialisation

What are the three protective layers of the meninges and their roles?

dura mater (outer, tough, structural support), arachnoid mater (middle, web-like, contains CSF), pia mater (inner, delicate, adheres to brain, nutrient supply)

What is the function of cerebrospinal fluid (CSF)?

cushions the brain, maintains intracranial pressure, delivers nutrients, removes waste, circulates via arterial pulsation and ependymal cell cilia

What characterizes gray matter in the brain?

contains neuronal cell bodies, dendrites, unmyelinated axons, glial cells; involved in cognition, sensory and motor functions

What characterizes white matter in the brain

contains myelinated axons and oligodendrocytes; responsible for fast electrical signal transmission and inter-region communication

What are the normal roles of astrocytes?

support neurons, maintain BBB, regulate extracellular ion balance, repair, and form glial scars after injury

What are the normal roles of microglia?

resident macrophages of the CNS; perform immune surveillance, phagocytose debris, and modulate synapses

How do microglia respond to CNS injury?

they become activated (larger body, shorter processes), phagocytose debris, and release inflammatory mediators

What is the impact of limited regenerative capacity in the brain?

injury may cause permanent loss of function due to post-mitotic neurons and inability to regenerate tissue effectively

What is cerebral edema and its types?

swelling in the brain, TYPES include cytotoxic (Na-K pump failure), vasogenic (BBB breakdown), congestive (capillary dilation)

What is the blood-brain barrier (BBB)?

a semi-permeable barrier formed by endothelial tight junctions and astrocyte foot processes, regulating entry of substances into CNS

What are perivascular spaces and their function?

fluid-filled spaces around blood vessels that house immune cells and mediate immune-CNS interactions, key in neuroinflammation

What is neuroinflammation and how is it classified?

inflammatory response in CNS, triggered by pathogens, toxins, autoimmune reactions. Classified as acute, sub-acute, or chronic

How does multiple sclerosis (MS) affect myelination?

autoimmune attack on CNS myelin leads to demyelination, impaired nerve conduction, and formation of hard plaques

What are histological findings in MS?

perivascular lymphocytes, reactive astrocytes, foam macrophages, loss of myelin (Luxol fast blue staining), demyelinated plaques

What is the role of microglia in MS?

act as phagocytes engulfing damaged myelin, appear as foamy macrophages due to lipid accumulation.

What are the risk factors for MS?

females, low vitamin D, family history, HLA-DR2, EBV infection, gut microbiome

What is the mechanism of Fingolimod in MS treatment?

traps lymphocytes in lymph nodes by modulating S1P receptor, reducing CNS inflammation and relapse frequency

What are the beneficial and detrimental effects of neuroinflammation?

beneficial - clears pathogens and debris, detrimental - causes tissue damage, synapse loss, chronic disease progression

How does neuroinflammation vary by disease?

acute (e.g., meningitis), subacute/chronic (e.g., MS), chronic with intact BBB (e.g., Alzheimer's), with varying levels of inflammation and BBB disruption

What cells mediate neuroinflammation?

microglia, astrocytes, infiltrating leukocytes releasing cytokines, chemokines, and ROS

What is meningitis vs encephalitis?

meningitis - inflammation of leptomeninges, encephalitis - inflammation of brain parenchyma (Meningoencephalitis = both.)

What is the pathology of Herpes Simplex Encephalitis (HSE)?

HSV-1 infection, preferentially affects temporal and frontal lobes, causes hemorrhagic necrosis, severe edema, and perivascular lymphocytic infiltration

What are histological features of viral encephalitis?

microglial nodules, perivascular cuffing, monocyte infiltration, reactive astrocytes, detectable viral antigen by IHC or PCR

What is the role of microglia in Herpes Simplex Encephalitis?

likely protective; microglial depletion increases viral replication and disease severity in models

What is the macro-pathology of Alzheimer's disease?

brain atrophy (especially temporal lobe), widened sulci, narrowed gyri, dilated ventricles

What are histological hallmarks of Alzheimer's disease?

amyloid plaques (beta-amyloid), neurofibrillary tangles (tau), and cerebral amyloid angiopathy in 80-90% of cases

How does neuroinflammation contribute to Alzheimer's disease?

astrocytes and microglia respond to plaques by releasing inflammatory mediators, surrounding plaques, and phagocytosing synapses

What is the dual role of microglia in Alzheimer's?

protective - clear amyloid, harmful - synapse pruning, cytokine release, exacerbates pathology

What is the role of astrocytes in Alzheimer's?

surround plaques, may wall off amyloid, become reactive, secrete cytokines, may convert to neurotoxic A1 type

What is the link between COVID and Alzheimer's pathology?

some COVID cases show amyloid-like plaques post-mortem, possibly related to hypoxia, but no increased tau pathology observed