Involvement of Calcium, Lipolytic Enzymes, and Free Fatty Acids in Ischemic Brain Trauma

Farooqui, Akhlaq A.; Hirashima, Yutaka; Farooqui, Tahira; Horrocks, Lloyd A.

doi:10.1007/978-1-4615-3312-2_7

Cited by 6 publications

(1 citation statement)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Free fatty acids have a direct effect on the Na÷/K + ATPase and on the release and uptake of the excitatory neurotransmitter glutamate. Arachidonic acid is a precursor for synthesis of eicosanoids, which are also thought to play a part in the process of cell death through various free-radical reactions (Bazan 1989;Traytsman et al 1991;Farooqui et al 1992).…”

Section: Metabolic Responses To the Excitotoxic Triggermentioning

confidence: 99%

Neuropathology and pathogenesis of mitochondrial diseases

Brown

Squier

1996

J of Inher Metab Disea

View full text Add to dashboard Cite

The majority of patients with mitochondrial disease have significant neuropathology, with the most common features being spongiform degeneration, neuronal loss and gliosis. Although there is considerable overlap between different mitochondrial diseases, the nature and distribution of the lesions is sufficiently distinctive in some cases to suggest a specific diagnosis. On the other hand, a number of different defects in cerebral energy metabolism are associated with common patterns of neuropathology (e.g. Leigh syndrome), suggesting that there is a limited range of responses to this type of metabolic disturbance. There are many descriptions of neuropathological changes in patients with mitochondrial disease, but there has been remarkably little investigation of the underlying pathogenic mechanisms. Comparisons with other conditions of cerebral energy deprivation such as ischaemia/hypoxia and hypoglycaemia suggest a possible role for excitotoxicity initiated by excitatory amino acid neurotransmitters. An additional contributing factor may be peroxynitrite, which is formed from nitric oxide and the oxygen free radicals which accumulate with defects of the mitochondrial electron transport chain. Mitochondrial diseases are often characterized by episodes of neurological dysfunction precipitated by intercurrent illness. Depending on the severity of the metabolic abnormality, each of these episodes carries a risk of further neuronal death and the result is usually progressive accumulation of irreversible damage. The balance between reversible functional impairment and neuronal death during episodes of metabolic imbalance is determined by the effectiveness of various protective mechanisms which may act to limit the damage. These include protective metabolic shielding of neurons by astrocytes and suppression of electrical activity (and hence energy demands) by activation of ATP-gated ion channels. In addition, recent evidence suggests that lactic acid, the biochemical abnormality common to these conditions, may not be toxic at moderately high concentrations but may in fact be protective by reducing the sensitivity of neurons to excitotoxic mechanisms.

show abstract

Section: Metabolic Responses To the Excitotoxic Triggermentioning

confidence: 99%