Ischemic damage

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

An amiloride analog that inhibits Na+/H+ ion exchangers and is under consideration for the prevention of post-ischemic damage. 

Evaluation of inhibition of the other isoforms is still in the preclinical stages. Inhibition of NHE2 with prostaglandin E2 or with amiloride hastens the reestablishment of barrier function after intestinal ischemic damage in pigs and the use of S-3226 in rats with renal ischemia improved outcomes. Further work examining the effect of inhibition of the other isoforms is still required. 

Findings obtained from experimental studies suggest that induction of iNOS mediates inflammatory or ischemic brain damage and that excessively activated nNOS under excitotoxic or ischemic conditions produces NO that is toxic to surrounding neurons. Selective inhibition of iNOS or nNOS may be neuroprotec-tive. This is also the case in glaucoma and diabetic... 

With modest impairment of blood flow, this mechanism allows for preservation of oxidative metabolism without alteration in electrical function. However, when CPP and therefore CBF are sufficiently low, OEF reaches a maximum and cannot increase further. Brain tissue ceases to function electrically, resulting in a neurologic deficit. Microvascular collapse occurs, and CBV falls. If the oxygen supply falls low enough, the tissue dies. Of critical clinical importance is the observation that the amount of time it takes for tissue to suffer irreversible damage is inversely related to the severity of the ischemic insult. Tissue that is completely deprived of blood will die within a few minutes, but less severely hypoperfused tissue may survive for many hours, and may be saved by timely thrombolysis that restores perfusion, or perhaps by another therapeutic intervention. 

Barth A, Barth L, Newell DW. Combination therapy with mk-801 and alpha-phenyl-tert-butyl-nitrone enhances protection against ischemic neuronal damage in organotypic hippocampal slice cultures. Exp Neurol 1996 141 330-336. 

Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ. Coohng for acute ischemic brain damage (cool aid) an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001 32 1847-1854. 

De GeorgiaMA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M, Davis SM, Koroshetz WJ, Rordorf G, Warach S. Cooling for acute ischemic brain damage (cool aid) a feasibility trial of endovascular cooling. Neurology 2004 63 312-317. 

PulsineUi WA, Waldman S, Rawhnson D, Plum F. Moderate hyperglycemia augments ischemic brain damage a neuropathologic study in the rat. Neurology 1982 32(11) 1239-1246. 

Tso and Lam suggested that astaxanthin could be useful for prevention and treatment of neuronal damage associated with age-related macular degeneration and may also be effective in treating ischemic reperfusion injury, Alzheimer s disease, Parkinson s disease, spinal cord injuries, and other types of central nervous system injuries. Astaxanthin was found to easily cross the blood-brain barrier and did not form crystals in the eye. 

Lactate dehydrogenase (LDH) is a nonspecific marker of hepa-tocyte damage disproportionate elevation of LDH indicates ischemic injury. 

---