Altered mechanisms of motor-evoked potential generation after transient focal cerebral ischemia in the rat: implications for transcranial magnetic stimulation

We recently demonstrated that a long-lasting transmission defect in cortica l synapses caused motor dysfunction after brief middle cerebral artery (MCA ) occlusion in the rat despite rapid recovery of axons. In this experimenta l study, we have examined the impact of differential recovery of synapses a nd axons on generation of motor-evoked potentials (MEP) recorded from contr alateral paralyzed and ipsilateral unaffected muscles, to gain insight into mechanisms of MEPs recorded from stroke patients by transcranial magnetic stimulation (TMS). MEPs generated by focal electrical stimulation of the fo relimb area of motor cortex were simultaneously recorded from the brain ste m, contra- and ipsilateral forelimb and contralateral hindlimb muscles in r ats subjected to transient MCA occlusion. The effect of ischemia on cortica l activity and axonal conduction was differentially studied by proximal or distal occlusion of the MCA. Regional cerebral blood flow changes in the fo relimb area were monitored by laser-Doppler flowmetry during ischemia and r eperfusion. Lo addition, synaptic transmission within the forelimb area of motor cortex was examined by intracellular and extracellular recording of p otentials generated by stimulation of the premotor area. No MEP response wa s recorded during ischemia. Upon reperfusion: (i) motor axons readily regai ned their excitability and cortical stimulation caused successive pyramidal volleys (recorded as D waves from the brain stem) and a MEP from contralat eral paralytic muscles although synaptic activation of motor pathways was n ot feasible; (ii) the amplitude of pyramidal volley was increased; (iii) ME Ps with a longer latency were recorded from the ipsilateral forelimb. In co nclusion, differential recovery of synapses and axons after ischemia may ac count for some previously unexplained findings (such as preserved MEPs in p aralysed muscles) observed in cortical stimulation studies of stroke patien ts. (C) 2000 Elsevier Science B.V. All rights reserved.