Depressed cortical excitability and elevated matrix metalloproteinases in remote brain regions following intracerebral hemorrhage.
The absence of cortical responses to external stimuli is a dubious clinical sign during the first 1-2 days of brain injury. We previously showed that the amplitude of the somatic evoked potential (SEP) in the swine is diminished at the infarct site and perihematomal surround within the first 6 h of collagenase-induced intracerebral hemorrhage (ICH). We now report that this depressed SEP persists during the subchronic (48 h) period of ICH in the swine not only within the injured primary somatosensory (SI) cortex, but also in the contralateral homotopic SI cortex. This impairment of sensory responsiveness was accompanied by increases in various matrix metalloproteinases (MMPs) in different brain regions. By 24 h, a marked rise in MMP-9, an inflammatory marker, was detected in the white matter of the ipsilesional SI and secondary somatosensory cortex (SII), and in the contralesional SI gray matter, as compared to saline-injected controls. A subsequent increase in MMP-9 level was found in the ipsilesional SI and SII gray matter, and in the contralesional SI white matter by 48 h (P<0.05). By 7 days, significant levels of MMP-9 were detected only in the ipsilesional SI white and gray matter tissues. In contrast, the elevation of MMP-2, a marker of degeneration, was delayed until 7 days post-ICH in the ipsilesional SII gray matter. A significant rise in MMP-9 was also noted in CA1 of the ipsilesional and contralesional hemispheres during 1-2 days. Our MMP assay shows that the depressed cortical excitability seen in the contralateral SI cortex is a manifestation of the broad effect of a focal ICH that produces inflammatory and degenerative processes not only in the region adjacent to the focal ICH site, but also in remote regions that are functionally connected to the site of focal ICH.
Department of Neurology, University of New Mexico Health Science Center, 915 Camino de Salud, Albuquerque, NM 87131, USA. munbryce@unm.edu
Sheila
S
Mun-Bryce
Arika
A
Wilkerson
Bernadette
B
Pacheco
Tongsheng
T
Zhang
Seema
S
Rai
Yaozhi
Y
Wang
Yoshio
Y
Okada
D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology* / Q000528:radiation effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology*; D017364:Collagenases; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004566:Electrodes; D004586:Electrophoresis / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology* / Q000528:radiation effects; D013552:Swine; D013997:Time Factors
D017364:Collagenases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9