Makindo Medical Notes

Related Subjects: |Brain Herniation syndromes |Haemorrhagic stroke |Traumatic Head/Brain Injury |Acute Hydrocephalus |Epidural Haematoma |Subdural haematoma |Basic Neuroscience |Medulla Oblongata |Midbrain |Pons |Caudate Nucleus |Putamen and Globus Pallidus |Cerebral Cortex |Internal Capsule |Cavernous sinus |Basal Ganglia

Cells in the CNS

A comprehensive understanding of stroke necessitates a deep knowledge of brain anatomy, physiology, and pathophysiology. The brain is an intricate structure with around 10¹¹ neurons and an even larger number of glial cells, outnumbering neurons by 10 to 50 times. Although neurons are central to brain function, they form only a fraction of the brain's cellular composition. Nearly 40% of the human genome contributes to the brain's intricate development and function. The efficiency of neurons in maintaining excitability is dependent on a continuous supply of ATP through oxidative phosphorylation, emphasizing the brain's metabolic demand.

The brain consists of two primary types of cells: neurons and glial cells. A thorough understanding of these cells' structure and functions is crucial, especially when studying conditions like stroke. Additionally, the concept of the neurovascular unit, which includes neurons and supporting cells, is key to understanding the mechanisms underlying stroke and other brain injuries.

Neuronal Cells

Neurons are the brain's primary "information processing" units, playing critical roles in receiving sensory input, processing data, and generating output signals. Neuronal cell bodies are concentrated in areas known as grey matter (such as the cortex, subcortical nuclei, brainstem, and cerebellum). Neurons come in various types and sizes, from the Purkinje cells in the cerebellum, known for their complex dendritic trees, to the specialized cells of the retina and the auditory system.

Each neuron is composed of a cell body (soma), which houses the nucleus and essential organelles like mitochondria, Golgi apparatus, and ribosomes. Dendrites extend from the soma to receive inputs from other neurons. If the sum of these inputs reaches a threshold, an action potential is initiated at the axon hillock. This electrical impulse travels along the axon to the axon terminals, where neurotransmitters are released into the synaptic cleft to communicate with subsequent neurons.

Neuronal communication relies on anterograde transport (movement of molecules like neurotransmitters from the soma to the axon terminal) and retrograde transport (movement from axon terminals back to the soma). These processes are crucial for maintaining neuronal function and are implicated in various neurological conditions, such as how pathogens like rabies and tetanus utilize retrograde transport to reach the CNS.

Non-Neuronal Cells

Glial cells, deriving from the Greek word for "glue," play supportive roles in the CNS. Far more than structural components, they maintain the CNS environment, support repair processes after injury, and form protective barriers like the blood-brain barrier.

• Astrocytes: The most numerous glial cells, star-shaped astrocytes provide structural scaffolding, regulate ion balance, and maintain the blood-brain barrier. They store glycogen and are crucial in neurotransmitter recycling, such as glutamate, and in buffering potassium levels.
• Microglia: The CNS's resident immune cells, these cells act as macrophages, engulfing and clearing debris, dead cells, and pathogens. Microglia are pivotal in the brain's response to infection or injury, modulating inflammation and immune reactions.
• Ependymal Cells: These ciliated cells line the ventricles of the brain, facilitating the flow of cerebrospinal fluid (CSF). They play a role in maintaining the homeostasis of the CSF environment and can be a source of ependymomas, a rare type of brain tumor.
• Oligodendrocytes: Responsible for myelinating axons in the CNS, oligodendrocytes increase the speed of nerve conduction via saltatory conduction. A single oligodendrocyte can myelinate multiple axons, unlike Schwann cells in the peripheral nervous system.

Cell Electrophysiology

The brain's processing abilities hinge on the electrical properties of neurons, particularly the resting membrane potential and action potential. The resting membrane potential is the charge difference across the neuronal membrane at rest, typically around -70 mV, due to selective ion permeability and the activity of ion pumps like the sodium-potassium pump.

Upon stimulation, a neuron's membrane potential becomes more positive. When this depolarization reaches a threshold, an action potential is triggered. This involves a rapid influx of sodium ions through voltage-gated sodium channels, followed by potassium efflux, which repolarizes the membrane. This electrical impulse propagates along the axon, enabling synaptic communication.

Myelinated axons conduct action potentials more rapidly due to saltatory conduction, where the signal jumps between nodes of Ranvier. This efficient mode of conduction is compromised in demyelinating conditions like multiple sclerosis, resulting in slowed or disrupted nerve transmission.

Synapses, Neurotransmitters, and Receptors

Synaptic transmission can be either excitatory or inhibitory, depending on the neurotransmitters released and the receptors involved. Major neurotransmitters include:

• Glutamate: The primary excitatory neurotransmitter in the CNS, acting on NMDA and AMPA receptors.
• GABA: The main inhibitory neurotransmitter, interacting with GABA_A and GABA_B receptors to dampen neuronal excitability.
• Acetylcholine: Acts at both nicotinic (ionotropic) and muscarinic (metabotropic) receptors, playing roles in both excitation and inhibition depending on the receptor subtype.
• Monoamines: Include dopamine, serotonin, and norepinephrine, each with distinct roles in mood regulation, cognition, and arousal.

Synaptic plasticity, the ability of synapses to strengthen or weaken over time, is fundamental for learning and memory. This adaptability involves changes in receptor density and neurotransmitter release, allowing synapses to adapt to increased or decreased activity.

Brain Physiology and Cerebral Perfusion

Despite making up only 1-2% of body weight, the brain requires about 15% of cardiac output and 20% of the body's oxygen. This high metabolic demand is met primarily through glucose oxidation. The brain lacks significant energy reserves, making it vulnerable to any interruption in its blood supply.

Autoregulation ensures stable cerebral blood flow, adjusting vessel diameter in response to fluctuations in blood pressure, carbon dioxide levels, and pH. This mechanism is critical during events like stroke, where localized ischaemia disrupts blood flow to parts of the brain.

Stroke Pathophysiology

Stroke results from a sudden interruption in cerebral blood flow, leading to neuronal death. The affected area is classified into three zones:

Time is critical in stroke management. Early intervention can save the penumbra, reducing the extent of permanent brain injury. Techniques like MRI-DWI help differentiate the ischemic core from at-risk tissue, guiding therapies like thrombolysis or thrombectomy.

Factors Influencing Brain Injury in Stroke

References

• Neuroanatomy, Action Potential - StatPearls
• Cerebral Blood Flow and Metabolism in Stroke - PMC