Journal of neurotrauma
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Journal of neurotrauma · Jan 2005
The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats.
This report compares the effects of progesterone and its metabolite, allopregnanolone, on the early injury cascade (apoptosis) and long-term functional deficits after TBI. Progesterone (16 mg/kg) or allopregnanolone (4, 8, or 16 mg/kg) were injected at 1 h, 6 h, and then for 5 consecutive days after bilateral contusions of the frontal cortex in adult male rats. Within one day after injury, progesterone and allopregnanolone reduced both the expression of pro-apoptotic proteins caspase-3 and Bax, and apoptotic DNA fragmentation. ⋯ Compared to sham-operated controls at 19 days after injury, injured rats given either progesterone or any of three doses of allopregnanolone had equivalent numbers of ChAT-positive cells in the nucleus basalis magnocellularis. At 19 days post-injury, rats given progesterone or allopregnanolone (8 mg/kg) showed improved performance in a spatial learning task compared to injured rats given only the vehicle. These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone and allopregnanolone and help to explain why better cognitive performance is observed after injury when animals are given either neurosteroid.
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Journal of neurotrauma · Dec 2004
Small volume resuscitation with HyperHaes improves pericontusional perfusion and reduces lesion volume following controlled cortical impact injury in rats.
The hyperosmolar and hyperoncotic properties of HyperHaes (HHES) might improve impaired posttraumatic cerebral perfusion. Possible beneficial effects on pericontusional perfusion, brain edema, and contusion volume were investigated in rats subjected to controlled cortical impact (CCI). Male Sprague-Dawley rats (n = 60) anesthetized with isoflurane were subjected to a left temporoparietal CCI. ⋯ HHES significantly improved cortical perfusion at 4 h after CCI, approaching baseline values (85 +/- 12%). While increased posttraumatic brain edema was not reduced by HHES at 24 h, cortical contusion volume was significantly decreased in the HHES-treated rats at 7 days after CCI (23.4 +/- 3.5 vs. 39.6 +/- 6.2 mm3; p < 0.05). Intravaneous administration of HHES within 15 min after CCI has a neuroprotective potential, as it significantly attenuated impaired pericontusional perfusion and markedly reduced the extent of induced structural damage.
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Journal of neurotrauma · Dec 2004
Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy.
Recent experimental data have shown that levels of matrix metalloproteinase-9 (MMP-9) increase after traumatic brain injury (TBI), degrading components of the basal lamina disrupting the blood-brain barrier. However, the post-traumatic secretion patterns of MMP-9 in humans are unknown. We measured the concentration of MMP-9 in plasma after TBI at the same time as the concentration of interleukin-6 (IL-6) in serum. ⋯ These results indicate that MMP-9 is elevated in patients with acute TBI, and may play an important role in traumatic brain damage. The elevation of MMP-9 is associated with inflammatory events following TBI. Hypothermic intervention may suppress the elevation of MMP-9 with suppression of the inflammatory response, affording neuroprotection in TBI.
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Journal of neurotrauma · Dec 2004
Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.
Oxidative stress is a significant contributor to the secondary sequelae of traumatic brain injury (TBI), and may mediate subsequent neurobehavioral deficits and histopathology. The present study examined the neuroprotective effects of bromocriptine (BRO), a dopamine D2 receptor agonist with significant antioxidant properties, on cognition, histopathology, and lipid peroxidation in a rodent model of focal brain trauma. BRO (5 mg/kg) or a comparable volume of vehicle (VEH) was administered intraperitoneally 15 min prior to cortical impact or sham injury. ⋯ TBI increased MDA in all examined regions of the VEH-treated, but not BRO-treated group versus SHAMs. MDA was significantly decreased in both the striatum (4.22 +/- 0.52 versus 5.60 +/- 0.44 nmol per mg/tissue +/- SEM) and substantia nigra (4.18 +/- 0.35 versus 7.76 +/- 2.05) of the TBI+BRO versus TBI+VEH groups, respectively, while only a trend toward decreased MDA was observed in the frontal cortex (5.44 +/- 0.44 versus 6.96 +/- 0.77). These findings suggest that TBI-induced oxidative stress is attenuated by acute BRO treatment, which may, in part, explain the benefit in cognitive and histological outcome.
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Journal of neurotrauma · Nov 2004
Comparative Study Clinical TrialGFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome.
Research indicates that glial fibrillary acidic protein (GFAP), part of the astroglial skeleton, could be a marker of traumatic brain injury (TBI). S100B, an astroglial protein, is an acknowledged marker of TBI. Our goal was to analyze the relationship of GFAP/S100B to brain damage and outcome, and to compare the accuracy of GFAP/S100B for prediction of mortality after TBI. ⋯ S100B was lower in focal lesions of <25 mL than in non-evacuated mass lesions (p < 0.0005) and lower in swelling than in shifts of >0.5 cm (p < 0.005). GFAP and S100B were lower in ICP < 25 than ICP > or = 25 (p < 0.0005), in CPP > or = 60 than CPP < 60 (p < 0.0005), in MAP > 70 than MAP < or = 70 mm Hg, and in GOS 4-5 than GOS 1 (p < 0.0005). Both measurement of GFAP and S100B is a useful non-invasive means of identifying brain damage with some differences based on the pattern of TBI and accompanying multiple trauma and/or shock.