Neuronal injury

Disorders of protein synthesis and water-electrolyte balance

Normal nerve cell function is impossible without continuous protein synthesis. Amino acid deficiency, decreased enzyme activity, or destruction of the endoplasmic reticulum (Nissl substance) lead to irreversible damage. Similar failures occur in glial cells as well—for instance, in astrocytes responsible for pinocytosis.

Functional and structural changes often begin with impaired operation of plasmalemma ion channels. A pathological cycle develops:

1. Neurons rapidly lose potassium ions (K⁺), which accumulate in the extracellular environment.
2. Sodium ions (Na⁺) are retained inside the cell.
3. Water rushes into the cell following sodium along the osmotic pressure gradient.
4. Hyperosmia, hyperhydration, and severe swelling occur, which inevitably leads to the destruction of the neuron.

At the level of the whole organism, neurological dysfunctions can manifest as various systemic failures, such as hyporexia (decreased appetite), hyposalivation (lack of saliva), and gastric hyposecretion.

Role of calcium and the glutamate cascade

A crucial irreversible stage of alteration is the accumulation of an excessive amount of Ca²⁺ ions in the cytoplasm. This is facilitated by neurotransmitter imbalance, primarily an excess of glutamate, which is massively released during ischemia.

Excess glutamate causes sustained overactivation of NMDA receptors. This opens membrane channels, and calcium rushes inside in an avalanche-like manner. Sustained depolarization of the plasmalemma occurs, causing the cell to no longer perform its function. Inside the neuron, excess calcium activates destructive enzymes:

• Protein kinase C disrupts protein phosphorylation processes.
• Phospholipase cleaves membrane phospholipids, which additionally releases calcium from intracellular stores.
• Endonuclease begins destroying nucleic acids.

Raging free-radical reactions complete the destruction process.

Neuronal membrane damage

Alteration of membrane structures is recognized as the universal mechanism of impaired neural activity. Membranes are destroyed under the influence of several factors:

• Generation of reactive oxygen species and enhancement of lipid peroxidation (LPO).
• Attack by activated endogenous phospholipases.
• Mechanical overstretching due to hyperhydration and swelling.
• Insertion of amphiphilic compounds into the bilayer lipid layer.

Fatal consequences of membrane damage: All cell vital activity is disrupted. Synaptic transmission and the synthesis of mediators (peptides, amino acids, catecholamines) fail, and axonal transport stops. The specific function of the neuron—electrogenesis—ceases. Ultimately, the cell dies.

Mechanisms and pathways of nerve cell death

The scenario by which a neuron dies depends on many factors: the intensity and duration of pathogen exposure, phylogenetic characteristics of the cell, selectivity of damage, and the state of the blood-brain barrier (BBB).

Two fundamentally different pathways of cell death are distinguished:

1. Necrosis (destruction). Develops during gross, massive damage and is usually accompanied by a breach of the BBB. Typical examples are ischemic or hemorrhagic strokes, where brain tissue is rapidly destroyed due to acute hypoxia and intracellular acidosis.
2. Genetically controlled death (apoptosis and necroptosis). Most commonly encountered in neurodegenerative pathologies. This pathway is characteristic of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and various types of dementias.

Class and exam questions

What else to study on this topic

• The role of astrocytes and pinocytosis in maintaining nervous tissue homeostasis
• Neurotransmitter metabolism: peptides, catecholamines, and amino acids
• Blood-brain barrier (BBB) dysfunction in brain tissue necrosis
• Forms of interneuronal interactions and afferent link disorders
• Intracellular acidosis as a damage factor in ischemia

Other topics in "Chapter 28. Standard forms of pathology of the nervous system"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.