title: Brain protection: physiological and pharmacological considerations. Part II: The pharmacology of brain protection.
abstract: Neuroprotective agents may exert their effect by reducing cerebral oxygen demand (CMRO2), increasing cerebral oxygen delivery, or by altering ongoing pathological processes. Barbiturates provide neuroprotection by reducing the CMRO2 necessary for synaptic transmission while leaving the component necessary for cellular metabolism intact. Isoflurane may exert a neuroprotective effect by a similar mechanism but its efficacy is likely less than that of barbiturates due to adverse effects on cerebral blood flow. Lidocaine reduces CMRO2 by affecting both cellular metabolic processes and synaptic transmission and thus resembles hypothermia in its mechanism of action. Benzodiazepines reduce CMRO2 by reducing synaptic transmission and their use as neuroprotectants produces less haemodynamic compromise than barbiturates. The mechanism of protection by calcium entry blocking agents appears to be due to improved blood flow as opposed to altering abnormal Ca++ fluxes. In contrast, agents such as ketamine and MK-801 may prevent abnormal Ca++ fluxes through their competitive interaction with N-methyl-D-aspartate receptors. Phenytoin prevents K(+)-mediated ischaemic events from progressing. Agents worthy of further investigation include corticosteroids, free radical scavengers, prostaglandin inhibitors and iron chelators.
authors.affiliation: Department of Anaesthesiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Murdoch
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000777:Anesthetics; D002121:Calcium Channel Blockers; D006993:Hypnotics and Sedatives