Journal of neurotrauma
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Journal of neurotrauma · May 2004
Activation of microglial cells and complement following traumatic injury in rat entorhinal-hippocampal slice cultures.
The complement cascade has been suggested to be involved in development of secondary brain damage following traumatic brain injury (TBI). Previous studies have shown that reactive microglia are involved in activation of the complement cascade following various injuries to the nervous system. Macrophages seem to have a significant role in this process, but it is still unclear whether these cells, as well as the complement components, are derived from reactive microglia or if these biological events only can occur as a result from the influx of plasma and monocytes via a disrupted blood-brain barrier (BBB). ⋯ In addition, Neurons (Neun-IR) near the injury were found to co-localize with clusterin-IR indicating upregulation of a defense system to the endogenous complement attack. The present study provides evidence that microglia and complement is activated in the injury border zone of the tissue slice in a similar fashion as in vivo following TBI, despite the absence of plasma/blood products and cells. These findings support the hypothesis that reactive microglia have a key role in complement activation following TBI by local synthesis of complement with a potential impact on development of secondary neuronal insults.
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Journal of neurotrauma · Mar 2004
Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig.
Inflicted brain injury is associated with widespread traumatic axonal injury (TAI) and subdural hematoma and is the leading cause of death in infants and children. Anesthetized 3-5-day-old piglets were subjected to either a single (n = 5) or double (n = 6, 15 min apart) rapid (<15 msec), non-impact, axial rotations of the head. Peak rotational velocities (averaging 172 rad/sec for single and 138 rad/sec for double loads) were lower than those utilized to induce severe injuries (240-260 rad/sec; Raghupathi and Margulies, 2002). ⋯ Although the density of injured axons did not significantly increase after two rotational loads, the distribution of injured axons shifted from a few foci (2.2 +/- 2.3 per animal) with 1-2 swellings/bulbs following a single rotation to significantly more foci (14.7 +/- 11.9), and additional foci (2.5 +/- 1.9) containing 3 or more axon swellings/bulbs following two rotational loads. The density and distribution of injured axons following a single mild rotation were significantly reduced compared with those obtained previously following a single more severe rotational load. Collectively, these data are indicative of the graded response of the immature brain to rotational load magnitude, and importantly, the vulnerability to repeated, mild, non-impact loading conditions.
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Journal of neurotrauma · Mar 2004
Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats.
Recent evidence indicates that estrogen exerts neuroprotective effects in both brain injury and neurodegenerative diseases. We examined the protective effect of estrogen on functional recovery after spinal cord injury (SCI) in rats. 17beta-estradiol (3, 100, or 300 microg/kg) was administered intravenously 1-2 h prior to injury (pre-treatment), and animals were then subjected to a mild, weight-drop spinal cord contusion injury. Estradiol treatment significantly improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. ⋯ Furthermore, 17beta-estradiol significantly increased expression of the anti-apoptotic genes, bcl-2 and bcl-x, after SCI while expression of the pro-apoptotic genes, bad and bax, was not affected by drug treatment. Finally, intravenous administration of 17beta-estradiol (100 microg/kg) immediately after injury (post-treatment) also significantly improved hind limb motor function 19-30 days after SCI compared to vehicle-treated controls. These data suggest that after SCI, 17 beta-estradiol treatment improved functional recovery in the injured rat, in part, by reducing apoptotic cell death.
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Journal of neurotrauma · Mar 2004
Subventricular zone neural stem cells remodel the brain following traumatic injury in adult mice.
Neural stem cells have recently been shown to contribute to the cellular remodeling that occurs following traumatic brain injury (TBI). Potential sources for these stem cells from within the brain include the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus. Using intraventricular injections of the fluorescent vital dye DiO in mice, we demonstrate that the subventricular zone population of stem cells can be reliably labeled and followed over time. ⋯ Using doublelabeling immunohistochemistry with anti-nestin, anti-GFAP, and anti-NeuN antibodies we demonstrate that labeled cells from the subventricular zone contribute primarily to the astroglial scar following injury. We do not observe any contribution to deeper areas of injury including the hippocampus. These data demonstrate that the subventricular zone contributes to brain remodeling following TBI, though neural stem cell sources outside the subventricular zone appear to play reparative roles as well.
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Journal of neurotrauma · Mar 2004
Induction of the stress response after inflicted and non-inflicted traumatic brain injury in infants and children.
Rapid induction of 72-kD heat shock protein (Hsp70) is a key component of the stress response and is seen after a variety of insults to the brain including experimental hyperthermia, ischemia, seizures, and traumatic brain injury (TBI). Little is known about the endogenous stress response in pediatric patients after brain injury. Accordingly, the concentration of Hsp70 was determined in 61 cerebrospinal fluid (CSF) samples from 20 infants and children after TBI. ⋯ These data suggest that the endogenous stress response, as measured and quantified by the Hsp70 concentration in CSF, occurs in infants and children after TBI. The endogenous stress response is more robust in victims of child abuse, compared with patients with accidental TBI, supporting age-dependence or a difference in either injury frequency, duration, severity, or mechanism in this subgroup of TBI patients. Further studies are needed to determine the role of Hsp70 in both non-inflicted and inflicted TBI in infants and children.