Journal of neurotrauma
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Journal of neurotrauma · Oct 2010
Effects of traumatic brain injury of different severities on emotional, cognitive, and oxidative stress-related parameters in mice.
Cognitive deficits and psychiatric disorders are significant sequelae of traumatic brain injury (TBI). Animal models have been widely employed in TBI research, but few studies have addressed the effects of experimental TBI of different severities on emotional and cognitive parameters. In this study, mice were subjected to weight-drop TBI to induce mild, intermediate, or severe TBI. ⋯ Intermediate and severe TBI caused extensive macroscopic and microscopic brain damage, while mild TBI typically had no histological abnormalities. Moreover, a significant increase in TBARS in the ipsilateral cortex and GPx in the ipsilateral hippocampus was observed at 24 h and 14 days, respectively, following intermediate TBI. The current experimental TBI model induced emotional and cognitive changes comparable to sequelae seen in human TBI, and it might therefore represent a useful approach to the study of mechanisms of and new treatments for TBI and related disorders.
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Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. ⋯ It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.
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Journal of neurotrauma · Oct 2010
Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.
Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. ⋯ Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.
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Journal of neurotrauma · Oct 2010
Injury-induced regulation of steroidogenic gene expression in the cerebellum.
Sex steroids assist adult neural tissue in the protection from and repair of damage resulting from neural injury; some steroids may be synthesized in the brain. Songbirds are especially useful models to explore steroidal neuroprotection and repair. First, the full suite of cholesterol transporters and steroidogenic enzymes are expressed in the zebra finch (ZF) brain. ⋯ Sex differences in response to the lesions were detected for TSPO, StAR, and aromatase. All birds responded to experimental conditions by showing time-dependent changes in the expression of TSPO, SCC, and aromatase, suggesting that acute trauma or stress may impact neurosteroidogensis for many days. These data suggest that the cerebellum is an active site of steroid synthesis in the brain, and each steroidogenic factor likely provides neuroprotection and promotes repair.
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Journal of neurotrauma · Oct 2010
Development of autonomic dysreflexia after spinal cord injury is associated with a lack of serotonergic axons in the intermediolateral cell column.
Autonomic dysreflexia consistently develops in patients and in rats after severe upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal sympathetic excitation. In this study we induced episodic hypertension in rats after varying degrees of SCI severity to investigate the contribution of serotonergic bulbospinal axons to the development of autonomic dysreflexia after SCI. Female Wistar rats (250-300 g) were used in all experiments in the following groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). ⋯ Intrathecal administration of the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin decreased resting MAP and was permissive to the colon distension-induced pressor response in SCI rats. These results suggest that the SCI-induced loss of serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that sparing of serotonergic axons beyond a critical threshold preserves cardiovascular regulation and prevents the development of autonomic dysreflexia.