Cerebral ischemia-hypoxia and biophysical mechanisms of neurodegeneration and neuroprotection effects

• Published in: Fiziolohichnyi zhurnal (Kiev, Ukraine : 1994) Ukraine : 1994), 2003, Vol.49 (2), p.7-12
• Main Author: Mahura, I S
• Format: Article
• Language: Ukrainian
• Subjects: Animals; Brain Ischemia - metabolism; Brain Ischemia - pathology; Calcium - metabolism; Calcium Channels - metabolism; Excitatory Amino Acid Antagonists - pharmacology; Humans; Hypoxia, Brain - metabolism; Hypoxia, Brain - pathology; Ion Channels - metabolism; Kainic Acid - metabolism; Nerve Degeneration - pathology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Oxygen - metabolism; Reactive Oxygen Species - metabolism; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Sodium - metabolism; Sodium Channel Blockers - pharmacology; Sodium Channels - drug effects; Sodium Channels - metabolism
• ISSN: 2522-9028

Neuronal responses to hypoxia-ischemia can be acute or chronic. In the early stages neuronal responses to ischemia-hypoxia are dependent on the modulation of ion channels. Acute responses relay mainly on O2-regulated ion channels which mediate adaptive changes in neuron excitability. Energy failure, an early consequence of hypoxia-ischemia, causes disruption of ionic homeostasis and accumulation of extracellular neurotransmitters. NMDA and AMPA/kainate receptors and Ca2+ channels contribute to excitotoxic neuronal degeneration. Excitotoxicity leads to increased Ca2+ influx, which can activate cytotoxic intracellular pathways. Reactive oxygen species (oxygen free radicals) generated during ischemia-reperfusion contribute to the injury. Oxygen free-radicals serve as important signalling molecules that trigger inflammation and apoptosis. Excitatory amino acid-receptor antagonists and Ca2+ channels blockers can provide neuroprotection in experimental models of hypoxia-ischemia but disrupt normal brain function. Because of their relative lack of behavioral side-effects, voltage-dependent Na+ channels blockers may have advantage over other neuroprotective mechanisms. The blockade of voltage-gated Na+ channels reduces the excitability of neurons, Na+ influx and the accumulation of intracellular Na+. These improve the ionic homeostasis and cellular energy levels and prevent ischemia-hypoxia induced neuronal injury and neuronal damage mediated by Ca2+ overload.