title: The role of taurine in cerebral ischemia: studies in transient forebrain ischemia and embolic focal ischemia in rodents.
abstract: Sudden cessation of blood flow to the brain results in a series of events that either result in rapid loss of brain cells or delayed neuronal injury in certain vulnerable regions of the brain. Research over the last three decades has allowed for a better understanding of how neurons and other brain cells die from the effects of ischemia and hypoxia in the central nervous system. Excitatory and inhibitory neurotransmitters exist in a very precise balance for normal function of the brain. Ischemia very rapidly disrupts this balance resulting in a rapid build-up of excitatory neurotransmitters, especially glutamate in the extracellular space. The increased glutamate together with energy loss opens a number of different types of calcium and sodium channels resulting in the build-up of these ions in neurons, leading to cellular dysfunction and death. While most ischemia research has focused on antagonism of excitatory amino acids, there are some reports on enhancement and amplification of inhibitory responses in focal and global ischemia. The majority of work relates to potentiation of GABA, either endogenous or through GABA potentiating medications. Taurine has neuroinhibitory properties and may also have potential for neuroprotection in cerebral ischemia. This present review focuses on the role of taurine as a neuroprotective agent, possibly acting through several different inhibitory mechanisms. Taurine may inhibit neurotransmitter release and may result in normal intracellular osmolality. In transient global ischemia in gerbils, we studied in vivo microdialysis of amino acids before, during and after ischemia. We were able to show that taurine resulted in attenuation of glutamate during ischemia (however did not reach significance). In similar experiments, neuronal damage was assessed in the hippocampus. Our results show 48% damage in taurine treated animals, 60% in alanine treated animals and 69% in control groups (trend towards protection but again did not reach significance) Focal ischemia was induced by embolizing a thrombus into the distal internal carotid artery and origin of the middle cerebral artery. Again, in studies where we compared taurine to a placebo treated animal, there was no significant decrease in the amount of damage with taurine. There are reports in the literature that taurine may attenuate neuronal injury during ischemia. Our studies in two models of cerebral ischemia in rodents did not reveal neuronal protection. It is possible that higher doses or possibly prolonged use of taurine may show better results. Taurine may also potentially offer additive protective effects when used in combination with thrombolysis or other neuroprotective agents. Further studies are necessary to better understand the potential for taurine as a neuroprotective agent in cerebral ischemia.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D020766:Intracranial Embolism / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology*; D012377:Rodentia; D013654:Taurine / Q000502:physiology*
chemical_list: D013654:Taurine