Regulation of ischemic cell death by the lipoic acid-palladium complex, Poly MVA, in gerbils

Modulation of ischemic cell death can be accomplished via a multitude of mechanisms, such as quenching radical species, providing alternative energy sources, or altering glutamate excitation. Transient cerebral ischemia will induce apoptotic cell death selectively to hippocampal cornus ammon's field 1 of the hippocampus (CA I) pyramidal cells, while neighboring CA3 and dentate neurons are spared. Poly MVA is a dietary supplement based on the nontoxic chemotherapeutic lipoic acid-palladium complex (LAPd). LAPd is a liquid crystal that works in cancer cells by transferring excess electrons from membrane fatty acids to DNA via the mitochondria. Therefore, by its structural nature and action as a redox shuttle, it can both quench radicals as well as provide energy to the mitochondria. To understand the role of LAPd in regulating ischemic cell death, we studied Poly MVA. Male Mongolian gerbils were subjected to 5 min of bilateral carotid artery occlusion under a controlled temperature environment (37.0-38.0degreesC). Animals were injected with physiological saline or either 30, 50, or 70 mg/kg of Poly MVA every 24 h beginning immediately after the occlusion until being sacrificed on experimental day 4. Damage was evaluated by analyzing nesting behavior and conducting blinded measures of viable CA1 lengths. All Poly MVA treatment dosages significantly (p < 0.05) reduced hippocampal CA1 damage by 72 h. Nesting scores were significantly improved after 30 and 50 mg/kg treatment but not 70 mg/kg. While nesting is usually a very accurate indicator of morphological damage, the 70 mg/kg-treated animals demonstrated excessive energy, thus ignoring the nesting material. While numerous routes offer varying degrees of CA1 neuronal survival after transient global ischemia, only the LAPd complex, which quenches radicals and provides energy to stabilize the mitochondria, offers such significant protection. Thus, the administration of Poly MVA may be a potent neuroprotective agent for victims of transient ischemic attack (TIA), cardiac arrest, anesthetic accidents, or drowning. (C) 2004 Elsevier Inc. All rights reserved.