TY - JOUR
T1 - Large cortical lesions produce enduring forelimb placing deficits in un-treated rats and treatment with NMDA antagonists or anti-oxidant drugs induces behavioral recovery
AU - Hoane, Michael R.
AU - Barbay, Scott
AU - Barth, Timothy M.
N1 - Funding Information:
This work was supported by the Texas Christian University Research Fund. The authors would like to thank Chris Raad for his help in completing the study.
PY - 2000/9/15
Y1 - 2000/9/15
N2 - Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl2), or the anti-oxidant N-tert-butyl-α-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl2 but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl2, or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats. Copyright (C) 2000 Elsevier Science Inc.
AB - Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl2), or the anti-oxidant N-tert-butyl-α-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl2 but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl2, or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats. Copyright (C) 2000 Elsevier Science Inc.
KW - Excitotoxicity
KW - Forelimb placing
KW - MK-801
KW - Magnesium chloride
KW - PBN
KW - Recovery of function
KW - Secondary brain damage
KW - Striatum
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U2 - 10.1016/S0361-9230(00)00327-0
DO - 10.1016/S0361-9230(00)00327-0
M3 - Article
C2 - 11044594
AN - SCOPUS:0034665388
SN - 0361-9230
VL - 53
SP - 175
EP - 186
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 2
ER -