Journal of neurotrauma
-
Journal of neurotrauma · Jul 2012
Comparative StudyThe relationship between localized subarachnoid inflammation and parenchymal pathophysiology after spinal cord injury.
Subarachnoid inflammation following spinal cord injury (SCI) can lead to the formation of localized subarachnoid scarring and the development of post-traumatic syringomyelia (PTS). While PTS is a devastating complication of SCI, its relative rarity (occurring symptomatically in about 5% of clinical cases), and lack of fundamental physiological insights, have led us to examine an animal model of traumatic SCI with induced arachnoiditis. We hypothesized that arachnoiditis associated with SCI would potentiate early parenchymal pathophysiology. ⋯ This was demonstrated by significant increases in cytokine (IL-1α and IL-1β) and chemokine (MCP-1, GRO/KC, and MIP-1α) production, MPO activity, blood-spinal cord barrier (BSCB) permeability, and MMP-9 activity. However, parenchymal inflammatory mediator production (acute IL-1α and IL-1β, subacute chemokines), BSCB permeability, and fibrous scarring in the PTS group were larger than the sum of the SCI group and arachnoiditis group combined, suggesting that arachnoiditis does indeed potentiate parenchymal pathophysiology. Accordingly, these findings suggest that the development of arachnoiditis associated with SCI can lead to an exacerbation of the parenchymal injury, potentially impacting the outcome of this devastating condition.
-
Journal of neurotrauma · Jul 2012
Incidence and risk factors for post-traumatic hydrocephalus following decompressive craniectomy for intractable intracranial hypertension and evacuation of mass lesions.
There continues to be a considerable interest in decompressive craniectomy in the management of severe traumatic brain injury (TBI). Though technically straightforward, the procedure is not without significant complications. In this study we assessed the incidence and risk factors for the development of subdural hygroma and hydrocephalus after decompressive craniectomy. ⋯ Maximum intracranial pressure prior to decompression (p=0.005), subdural hygroma (p=0.012), and a lower admission Glasgow Coma Scale score (p=0.009), were significant risk factors for hydrocephalus after decompressive craniectomy. Hydrocephalus requiring a VP shunt was associated with a higher risk of unfavorable neurological outcomes at 18 months (odds ratio 7.46; 95%CI 1.17,47.4; p=0.033), after adjusting for other factors. Our results showed a clear association between injury severity, subdural hygroma, and hydrocephalus, suggesting that damage to the cerebrospinal fluid drainage pathways contributes to the primary brain injury rather than the margin of the craniectomy as the factor responsible for these complications.
-
Journal of neurotrauma · Jul 2012
In vitro stretch injury induces time- and severity-dependent alterations of STEP phosphorylation and proteolysis in neurons.
Striatal-enriched tyrosine phosphatase (STEP) has been identified as a component of physiological and pathophysiological signaling pathways mediated by N-methyl-d-aspartate (NMDA) receptor/calcineurin/calpain activation. Activation of these pathways produces a subsequent change in STEP isoform expression or activation via dephosphorylation. In this study, we evaluated changes in STEP phosphorylation and proteolysis in dissociated cortical neurons after sublethal and lethal mechanical injury using an in vitro stretch injury device. ⋯ Blocking calpain activation in the initial 30 min after stretch injury increases the ratio of active STEP in cells and blocks STEP(33) formation, suggesting that STEP is an early substrate of calpain after mechanical injury. There is a strong correlation between the amount of STEP(33) formed and the degree of cell death observed after lethal stretch injury. In summary, these data demonstrate that previously characterized pathways of STEP regulation via the NMDA receptor are generally conserved in mechanical injury, and suggest that calpain-mediated cleavage of STEP(33) should be further examined as an early marker of neuronal fate after stretch injury.
-
Journal of neurotrauma · Jul 2012
Evaluation of a combined treatment paradigm consisting of environmental enrichment and the 5-HT1A receptor agonist buspirone after experimental traumatic brain injury.
Environmental enrichment (EE) and serotonin(1A) (5-HT(1A))-receptor agonists provide significant benefit after experimental traumatic brain injury (TBI). The aim of this study was to test the hypothesis that combining these therapies would produce an effect that is more robust than either therapy alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to EE or standard (STD) housing where they received either buspirone (0.3 mg/kg) or vehicle (1.0 mL/kg) once daily for 3 weeks. ⋯ These data show that EE and buspirone benefit functional outcome after TBI, but their combination is not more robust than either alone, which does not support the hypothesis. The lack of an additive effect may be due to the early-and-continuous EE paradigm on its own producing marked benefits, resulting in a ceiling effect. The evaluation of buspirone in a delayed-and-abbreviated EE paradigm is ongoing in our laboratory.
-
Journal of neurotrauma · Jul 2012
Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-κB pathway.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is effective in reducing axonal damage associated with traumatic brain injury (TBI), and has immunomodulatory properties. Toll-like receptor 4 (TLR4) is an important mediator of the innate immune response. It significantly contributes to neuroinflammation induced by brain injury. ⋯ Pretreatment with PACAP inhibited upregulation of TLR4 and its downstream signaling molecules MyD88, p-IκB, and NF-κB, and suppressed increases in the levels of the downstream inflammatory agents interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), in the brain tissue around the injured cortex and in the hippocampus. Administration of PACAP both in vitro and in vivo attenuated the ability of the TLR4 agonist lipopolysaccharide (LPS) to increase TLR4 protein levels. Therefore, PACAP exerts a neuroprotective effect in this rat model of TBI, by inhibiting a secondary inflammatory response mediated by the TLR4/MyD88/NF-κB signaling pathway in microglia and neurons, thereby reducing neuronal death and improving the outcome following TBI.