Introduction of the most common of these trauma-associated secondary

Brain Research 880 2000 38–50 www.elsevier.com locate bres Research report Distinctive amygdala kindled seizures differentially affect neurobehavioral recovery and lesion-induced basic fibroblast growth factor bFGF expression 1 2 ˜ Anthony E. Kline , Sylvia Montanez , Hallie A. Bradley, Courtney J. Millar, Theresa D. Hernandez Behavioral Neuroscience Program , Department of Psychology, University of Colorado, Campus Box 345, Boulder, CO 80309-0345, USA Accepted 25 July 2000 Abstract The differing effects of partial seizures on neurobehavioral recovery following anteromedial cortex AMC injury in rats have previously been reported. Specifically, convulsive Stage 1 seizures evoked ipsilateral to the lesion during the 6-day post-lesion critical period delayed recovery, while non-convulsive Stage 0 seizures were neutral. The present study was designed to elaborate on that research by examining several potential mechanisms for the seizure-associated difference observed in functional outcome. Anesthetized rats sustained unilateral AMC lesions followed by implantation of a stimulating electrode in the amygdala ipsilateral Expt. 1 or contralateral Expt. 2 to the lesion. Beginning 48 h after surgery, animals were kindled to evoke Stage 0 or Stage 1 seizure activity during the critical period. Kindling trials and afterdischarge AD were controlled to ascertain their role in functional outcome. Recovery from somatosensory deficits was assessed over a two-month period. The results revealed that i Stage 0 seizures did not impact recovery regardless of whether initiated ipsilateral or contralateral to the lesion, ii Stage 1 seizures prevented recovery only when initiated in the ipsilateral hemisphere during the post-lesion critical period, and iii the detrimental effect of Stage 1 seizures appears to be independent of the number of kindling trials provided and cumulative AD. Thus, to determine why Stage 1 seizures evoked in the hemisphere ipsilateral to the lesion impeded recovery, a separate group of animals Expt. 3 were kindled accordingly and processed for c-Fos and basic fibroblast growth factor bFGF immunohistochemistry. It was hypothesized that Stage 1 seizures evoked in the injured hemisphere prevent recovery by blocking lesion-induced bFGF expression in structures shown to be important for recovery after cortex lesions e.g., striatum. The results confirmed our hypothesis and suggest that the seizure-associated inhibition of lesion-induced bFGF may alter the growth factor-mediated plasticity necessary for functional recovery.  2000 Elsevier Science B.V. All rights reserved. Theme : Disorders of the nervous system Topic : Trauma Keywords : Anteromedial cortex; c-Fos; Immunohistochemistry; Growth factor; Trauma

1. Introduction of the most common of these trauma-associated secondary

events is the onset of seizures. Posttraumatic seizures Following brain insult, a diverse and complex series of PTS can be classified as either partial or generalized pathophysiological and behavioral events are initiated. One depending on whether the synchronous neuronal dis- charges remain localized or spread to both hemispheres, respectively. The latter have been shown in both the Corresponding author. Fax: 11-303-492-2967. clinical [2,31,33] and experimental [19,32,36,38] settings E-mail address : teridpsych.colorado.edu T.D. Hernandez. to exert differing effects on the recovering brain. Although 1 Present address: Brain Trauma Research Center, Department of Neuro- generalized seizures are seen in slightly less than half of surgery, University of Pittsburgh, 3434 Fifth Avenue, Suite 201, Pitts- PTS patients [76,80], empirical research has focused on burgh, PA 15260, USA. 2 this classification almost exclusively. Thus, to examine the Present address: Department of Pharmacology, University of Texas Health Sciences Center, San Antonio, TX 78284, USA. role of partial seizures on functional outcome, our labora- 0006-8993 00 – see front matter  2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 7 6 2 - 1 A .E. Kline et al. Brain Research 880 2000 38 –50 39 tory utilized a focal cortical injury model in conjunction Rowntree and Kolb [65] who exquisitely demonstrated that with electrical kindling of the amygdala, an animal model blocking this trophic factor retarded functional recovery of epileptogenesis [28]. Unilateral lesions of the anterome- following motor cortex lesions. dial cortex AMC produce an ipsilateral somatosensory The results of the present study provide at least one deficit. Recovery from this deficit has been found to be plausible mechanism for the distinct recovery patterns vulnerable to manipulation during the post-lesion ‘critical’ associated with Stage 0 and Stage 1 kindled seizures period, which has been defined as beginning at 12 h and following AMC lesions in rats. lasting for 6 days following lesion. That is, drugs or other experimental manipulations that impact the recovery pro- cess do so only when introduced within the first 6 days

2. Materials and methods common to all