Journal of neurotrauma
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Journal of neurotrauma · Jan 2010
Expression of protein phosphatase 2B (calcineurin) subunit A isoforms in rat hippocampus after traumatic brain injury.
Calcineurin (CaN) is a calcium/calmodulin-dependent phosphatase directly activated by calcium as a result of neuronal activation that is important for neuronal function. CaN subunit isoforms are implicated in long-term potentiation (LTP), long-term depression (LTD), and structural plasticity. CaN inhibitors are also beneficial to cognitive outcomes in animal models of traumatic brain injury (TBI). ⋯ There was also a significant alteration in the immunoreactivity of both CnA isoforms in the ipsilateral dentate gyrus, predominantly within the hidden blade. Alterations in CnA isoform regional distribution within the CA1, CA1-2, and dentate gyrus may have significant implications for persistent hippocampal dysfunction following TBI, including dysfunction in hippocampal plasticity. Understanding alterations in CnA isoform distribution may help improve the targeting of current therapeutic interventions and/or the development of new treatments for TBI.
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Journal of neurotrauma · Jan 2010
Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice.
There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated after acute brain injury, and that it may play an adaptive role in recovery through augmentation of cerebral blood flow (CBF). Through a series of experiments, we tested the hypothesis that the administration of BNP after different acute mechanisms of central nervous system (CNS) injury could improve functional recovery by improving CBF. C57 wild-type mice were exposed to either pneumatic-induced closed traumatic brain injury (TBI) or collagenase-induced intracerebral hemorrhage (ICH). ⋯ After ICH, mRNA polymerase chain reaction (PCR) and histochemical staining were performed during the acute injury phase (<24 h) to determine the effects on inflammation. Following TBI and ICH, administration of hBNP was associated with improved functional performance as assessed by rotorod and Morris water maze latencies (p < 0.01). CBF was increased (p < 0.05), and inflammatory markers (TNF-alpha and IL-6; p < 0.05), activated microglial (F4/80; p < 0.05), and neuronal degeneration (Fluoro-Jade B; p < 0.05) were reduced in mice receiving hBNP. hBNP improves neurological function in murine models of TBI and ICH, and was associated with enhanced CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel therapeutic strategy after acute CNS injury.
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Journal of neurotrauma · Dec 2009
Resuscitation of traumatic brain injury and hemorrhagic shock with polynitroxylated albumin, hextend, hypertonic saline, and lactated Ringer's: Effects on acute hemodynamics, survival, and neuronal death in mice.
Outcome after traumatic brain injury (TBI) is worsened by hemorrhagic shock (HS), but the optimal resuscitation approach is unclear. In particular, treatment of TBI patients with colloids remains controversial. We hypothesized that resuscitation with the colloids polynitroxylated albumin (PNA) or Hextend (HEX) is equal or superior to resuscitation with the crystalloids hypertonic (3%) saline (HTS) or lactated Ringer's solution (LR) after TBI plus HS in mice. ⋯ Also, 7-day survival was highest in the PNA group, but was not significantly different than the other groups. Ipsilateral hippocampal CA1 and CA3 neuron loss did not differ between groups. We conclude that the colloids PNA and HEX exhibited more favorable effects on acute resuscitation parameters than HTS or LR, and did not increase hippocampal neuronal death in this model.
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Journal of neurotrauma · Dec 2009
Acute hypoperfusion immediately after subarachnoid hemorrhage: a xenon contrast-enhanced CT study.
The acute neurological deficit present immediately after subarachnoid hemorrhage (SAH) correlates with overall outcome. Only limited data are available to quantify changes in cerebral perfusion in this acute phase, and this study sought to characterize those changes within the first 12 h post-SAH. Xenon contrast-enhanced CT scanning was performed in 17 patients (Hunt and Hess grade [HH] 1-3, n = 9; HH 4-5, n = 8) within 12 h after SAH. ⋯ Hemodynamic stress distribution was most pronounced in patients with higher HH grade (p < 0.05). The first 12 h after SAH are characterized by persistent, severe reduction of CBF, which in turn correlates with HH grade, but is independent of ICP or CPP. Acute peripheral vasospasm of the microvasculature, not detectable by conventional angiography, may account for this early phase of prolonged hypoperfusion.
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Journal of neurotrauma · Dec 2009
Abnormal corticospinal excitability in traumatic diffuse axonal brain injury.
This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (SP) duration. ⋯ In conclusion, our findings expand the concept that impairment of the excitatory and inhibitory phenomena in the motor cortex does not proceed in parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore, these data suggest that alterations in the corticospinal excitatory mechanisms are determined predominantly by the severity of DAI, and show a significant relationship with clinical motor dysfunction following severe trauma diffusely affecting the motor cortical connections. In severe TBI, motor and functional recovery might be linked to restitution of normal corticospinal mechanisms, indexed by normalization of the cortical excitability parameters.