ABSTRACT
Photothrombotic infarcts of the neocortex result in structural and functional alterations of cortical networks, including decreased GABAergic inhibition, and can generate epileptic seizures within 1 month of lesioning. In our study, we assessed the involvement and potential changes of cortical GABA A receptor (GABA AR) alpha1 subunits at 1, 3, 7, and 30 days after photothrombosis. Quantitative competitive reverse transcription-polymerase chain reaction (cRT-PCR) and semi-quantitative Western blot analysis were used to investigate GABA AR alpha1 subunit mRNA and protein levels in proximal and distal regions of perilesional cortex and in homotopic areas of young adult Sprague-Dawley rats. GABA AR alpha1 subunit mRNA levels were decreased ipsilateral and contralateral to the infarct at 7 days, but were increased bilaterally at 30 days. GABA AR alpha1 subunit protein levels revealed no significant change in neocortical areas of both hemispheres of lesioned animals compared with protein levels of sham-operated controls at 1, 3, 7, and 30 days. At 30 days, GABA AR alpha1 subunit protein expression was significantly increased in lesioned animals within proximal and distal regions of perilesional cortex compared with distal neocortical areas contralaterally (Student's t-test, p<0.05). Short- and long-term alterations of mRNA and protein levels of the GABA AR alpha1 subunit ipsilateral and contralateral to the lesion may influence alterations in cell surface receptor subtype expression and GABA AR function following ischemic infarction and may be associated with formative mechanisms of poststroke epileptogenesis.
Subject(s)
Cerebral Infarction/metabolism , Intracranial Thrombosis/metabolism , Neocortex/metabolism , Receptors, GABA-A/metabolism , gamma-Aminobutyric Acid/metabolism , Animals , Cerebral Infarction/chemically induced , Cerebral Infarction/genetics , Disease Models, Animal , Down-Regulation/genetics , Epilepsy/genetics , Epilepsy/metabolism , Epilepsy/physiopathology , Functional Laterality/physiology , Gene Expression/physiology , Intracranial Thrombosis/chemically induced , Intracranial Thrombosis/genetics , Lasers , Light Coagulation , Neocortex/blood supply , Neural Inhibition/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/genetics , Reverse Transcriptase Polymerase Chain Reaction , Rose Bengal , Synaptic Transmission/geneticsABSTRACT
The mechanisms of injured brain that establish poststroke seizures and epilepsy are not well understood, largely because animal modeling of these phenomena has had limited development. We studied the electrobehavioral properties of 2.5-month-old male Long-Evans rats by video-electroencephalogram (EEG) recordings during the 6 months following sham operation or lesioning by transient unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAO). The main findings of this study were: (1) control animals demonstrated interictal focal or restricted bilateral 7-8 Hz spike-wave discharges (SWDs) lasting 1-2 s without behavioral change and ictal generalized 7-8 Hz SWDs (absence seizures), which were prolonged, frequent, and associated with motor arrest of the animal; (2) lesioned animals demonstrated cortical infarction associated with interictal SWDs similar to controls, except that focal discharges were more numerous relative to bilateral discharges, and ictal SWDs, which were of shorter duration and less frequent than those of controls; (3) lesioned animals demonstrated decreased hemispheric and regional spectral power at approximately 7 and 15 Hz compared with controls, directly related to the reduced occurrence of ictal SWDs; and (4) lesioning did not independently generate either focal or generalized epileptic seizures. These studies demonstrate distinct electrobehavioral properties of Long-Evans rats lesioned by MCA/CCAO as juveniles and monitored by video-EEG recordings during young adulthood but fail to provide evidence of poststroke seizures or epilepsy.
