Involvement of monocarboxylate transporters in the cross-tolerance between epilepsy and cerebral infarction: A promising choice towards new treatments.


Department of Neurosurgery, AnNing Branch Hospital, The 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu Province, 730070, China. Electronic address: [Email]


Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptative responses that provide a defense against additional stress from the same (tolerance) or other (cross-tolerance) stimuli. Such endogenous modulators mediate the tolerance induced by numerous sublethal physical and chemical stress factors, of which epileptic preconditioning (EPC) and mild global ischemia are two most important mutually protective actions. However, the evidence for the complicated underlying mechanisms involved in this neuroprotective effects are lacking. During hypoxia/ischemia (H/I) and intense neural activity, lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporters (MCTs) in central nervous system (CNS). The present study investigated whether ischemic preconditioning (IPC) or EPC can provide protection to CNS against epilepsy or cerebral infarction respectively through regulation of MCTs expression in vivo. Rats were subjected to transitory middle cerebral artery occlusion (MCAO) or kainic acid (KA) preconditioning protocol respectively, followed by KA induced epilepsy or lethal MCAO as well as lactate transportation inhibitor injection, with a subsequent evaluation of behavior and infarct volume as well as MCTs expression in rats brain. IPC reduced the severity of status epilepticus induced by KA injection and EPC reduce infarct volume resulted from lethal MCAO. However, lactate transport blocking attenuated this neuroprotective effect and MCTs expression followed the same variation trends. These findings demonstrate that MCTs dependent mechanism is involved in the cross-tolerance between epilepsy and cerebral infarction, provide a potential basis for the clinical treatment of patients with brain diseases characterized by epilepsy and H/I.


Cerebral infarction,Cross-tolerance,Epilepsy,Monocarboxylate transporters,Preconditioning,Rat,