Lecture 16 - CNS 2 Flashcards
What cells in the CNS respond to injury?
- Neurons
- Oligodendrocytes
- Astrocytes
- Microglial
What is neuronal injury?
- Neurons are terminally differentiated so the brain has limited capacity to replace them
- Neurons may suffer acute injury they require glucose and oxygen to meet the metabolic demand
- Neurons may suffer chronic injury; they are maintained for the lifetime of the individual
What happens during acute neuronal injury?
o Red neurons: ‘dying neurons’ neurons that have undergone irreversible injury due to an insufficient supply of oxygen and glucose
Red neurons typically exhibit shrinkage of the cytoplasm, a loss of Nissl substance, and clumping of the chromatin in the nucleus. They are a hallmark of acute neuronal injury and are often seen in conditions such as cerebral ischemia, hypoxia, and traumatic brain injury.
o Ischemic event
Nuclear pyknosis, shrinkage of cell body, loss of Nissi substance, disappearance of nucleolus and eosinophilia of cytoplasm occurs first.
Lastly, dissolution of the cell and phagocytosis of debris occurs
What occurs during subacute and chronic neuronal injury?
Degeneration
Loss associated with a particular groups of neurons - often by apoptosis
Reactive gliosis
Inflammation
Exotoxicity
Oxidative stress
What occurs during trans-synaptic/trans-neuronal degeneration?
A process in which neurons and their synapses degenerate as a result of damage or injury to other neurons with which they are connected through neural circuits. This process is a secondary consequence of an initial injury or disease process that affects a subset of neurons within a neural circuit.
Damaging event that interrupts the afferent input e.g., the effect of eye enucleation on cells of lateral genticulate neurons
What occurs during an axonal reaction?
o Morphologic change in cell body following damage to the axon
o Associated with the regeneration of the axon (through protein synthesis and axonal sprouting)
Enlargement and rounding the cell body
Displacement of the nucleolus
Dispersion of Nissl substance (chromatolysis)
What occurs during neuronal inclusions?
o Ageing (complex lipids, lipofuscin, proteins and carbohydrates)
o Viral infection
Neuronal inclusions are abnormal accumulations of proteins or other molecules within the cytoplasm or nuclei of neurons.
What occurs during intracytoplasmic inclusions?
o Neurofibrillary tangles (Alzheimer disease)
o Lewy bodies (Parkinson disease)
Intracytoplasmic inclusions are abnormal accumulations of substances within the cytoplasm of cells, including neurons.
How are oligodendrocytes affected by injury?
- Does not respond to injury but can be injured
- High potential for repair
o Pool of oligodendrocyte progenitors can replace the lost oligodendrocytes - Myelin damage DOES NOT mean oligodendrocyte loss
o Myelin can be replaced if damaged as long as oligodendrocytes survive
o Remyelination thinner than normal, shorter internodes
How are astrocytes affected by injury?
- When directly injured as a result of ischaemia, toxicity or acute inflammation cytoplasmic swelling occurs as result of failure of cellular and organelle pumps
- Reactive astrogliosis
o It is a conserved defence mechanism that regulates neuroinflammation, limits the site of damage by forming a perilesional barrier and compact glial scar with fibro meningeal and other glia cells and promotes post-injury neuronal function recovery - Most important histological indicator of CNS injury
- Hypertrophy and hyperplasia
o Up-regulation of GFAP synthesis
o Extension of processes
o Stimulated by cytokines produced by activated microglia
o Release by-products of increased biological activity (nitric oxide, glutamate); toxic to the environment
o May contribute to further injury
What are the phenotypes of astrocytes in response to injury?
- A1 astrocytes:
o Contributes to injury
o Loss of function
o Neuroinflammation - A2 astrocytes:
o Promote healing after ischemic injury
How are microglia affected by injury?
- Morphological phenotype is used to indicate distinct microglial functional states
- Phagocytic microglia-neuronal death
o Trauma
o Inflammation
o Neuronal necrosis
o Viral and bacterial infections
o In response to gliomas (malignant astrocyte tumour) - Activated in response to injury
- Rapid and graded
o The more severe the injury – the greater the activation - Microglia activated but not phagocytic:
o Damage but not death of neurons
o Proliferate
o Expresses CD4, MHC 1 AND 2 antigens, cell adhesion molecules
o Produces cytokines - Activated microglia become rounded phagocytic cells
o ONLY when neuronal death occurs
o Can be destructive or reparative
What are the major causes of CNS injury?
- Trauma brain injury
- Cerebrovascular disease
- Infection
- Demyelinating disease
- Degenerative disorders
- Metabolic abnormality
- Toxic and acquired metabolic diseases
- Tumours
What is traumatic brain injury (TBI)?
- An external force that exceeds the protective capacity of the brain
- Mechanical injury: compression, shearing, tearing, stretching
- Affecting neurons, axons, glia cells and blood vessels
- Trauma can cause:
o Skull fractures
o Parenchymal injuries
o Vascular injuries (e.g., haematoma)
What is parenchymal injury?
- Contusions (bruising) and lacerations (penetration or tear)
- Crest of gyri are most vulnerable
- Evidence of acute brain injury:
o Haemorrhage
o Axonal swelling close to or distant from the site of damage
o Inflammatory response
o Oedema - A blow to the surface of the brain resulting in lesion at
o Point of contact
o Diametrically opposed
o Both
What is vascular injury in the brain?
- Direct disruption of the blood vessel wall leading to haemorrhage
- Epidural = rapid
o Epidural hematoma is the collection of blood in the epidural space, which is the space between the dura mater and inner surface of the skull - Subdural = delayed
o Subdural hematoma is the collection of blood in the subdural space, meaning between the dura mater and the arachnoid mater. - Subarachnoid space
- Intraparenchymal
o Direct due to trauma
o Consequence of underlying condition
