Oligodendrocyte vulnerability following traumatic brain injury in rats

Abstract

Experimental and clinical findings demonstrate that traumatic brain injury (TBI) results in injury to both gray and white matter structures. The purpose of this study was to document patterns of oligodendrocyte vulnerability to TBI. Sprague Dawley rats underwent sham operated procedures or moderate fluid percussion brain injury. Animals were perfusion-fixed for quantitative immunohistochemical analysis at 3 (n=9) or 7 (n=9) days post-surgery. Within the ipsilateral external capsule and corpus callosum, numbers of APC-CC1 immunoreactive oligodendrocytes were significantly decreased at 3 or 7 days post-TBI compared to sham rats (p<0.03). At both posttraumatic survival periods, double-labeling studies indicated that oligodendrocytes showed increased Caspase 3 activation compared to sham. These data demonstrate regional patterns of oligodendrocyte vulnerability after TBI and that oligodendrocyte cell loss may be due to Caspase 3-mediated cell death mechanisms. Further studies are needed to test therapeutic interventions that prevent trauma-induced oligodendrocyte cell death, subsequent demyelination and circuit dysfunction.

Omega-3 Polyunsaturated Fatty Acid Supplementation Improves Neurologic Recovery and Attenuates White Matter Injury after Experimental Traumatic Brain Injury

“…In many TBI models, significant loss of oligodendrocytes was observed as soon as 3 days post injury in the external capsule and corpus callosum. 29,30 In addition, a reduction of myelin staining in these areas substantiated a loss of matured oligodendrocytes implicating the ongoing of demylination besides the demise of oligodendrocyte progenitor cells. Therefore, attenuation in oligodendrocyte degeneration should improve the prognosis of TBI.…”

Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes

“…Indeed, in a recent publication, oligodendrocyte cell death by apoptotic-dependent mechanisms was demonstrated after a moderate TBI injury. 84 These and other studies emphasize that, in addition to primary axonal damage, axonal demyelination may also underlie some of the more progressive consequences of TBI. Importantly, because myelination is critical to the normal role of axons in terms of the complex function of neuronal circuits, demyelination could underlie many of the long-term functional consequences of brain injury.…”

“…83, 84 These data indicate that delayed apoptotic cell death, as well as other programmed cell death mechanisms, currently being investigated in the laboratory could underlie some of these long-term consequences of brain injury.…”

“…Subsequent to TBI, evidence for local demyelination associated with these WM changes has also been emphasized. 29,32,39,84,192 In animals where survival has been allowed up to 1 year after TBI, significant evidence of WM atrophy and demyelination has been reported. 28,30,31,33 Demyelination can occur as a result of several mechanisms, including primary axonal damage and subsequent Wallerian degeneration or death of myelinating cells.…”

Hypothermia in Stroke Therapy: Systemic versus Local Application

“…However, another study in fetal sheep countered these results by showing that delayed cerebral hypothermia partially protects white mater after global cerebral ischemia by stimulating oligodendrocyte proliferation, reducing microglial induction, and restoring the amount and patern of expression of myelin basic protein, once again conirming the neuroprotective role of hypothermia toward oligodendrogenesis [129,130]. Moreover, researchers have found that hypothermia atenuates demyelination, trauma-induced oligodendrocyte cell death, and overall circuit dysfunction [131,132]. While a study in preterm fetal sheep found that TH was correlated with an overall reduction in the hypoxia-induced death of immature oligodendrocytes, hypothermia did not prevent the hypoxia-induced inhibition of oligodendrocyte proliferation in the periventricular white mater zone [133,134].…”