Journal of neurotrauma
-
Journal of neurotrauma · Feb 2018
Spatial and cellular expression patterns of Erythropoietin-Receptor and Erythropoietin during a 42 day post-lesional time-course after graded thoracic spinal cord impact lesions in the rat.
Erythropoietin (Epo) exhibits promising neuroregenerative potential for spinal cord injury (SCI), and might be involved in other long-term sequelae, such as neuropathic pain development. The current studies investigated the time courses and spatial and cellular patterns of Epo and erythropoietin receptor (EpoR) expression along the spinal axis after graded SCI. Male Long Evans rats received 100 kdyn, 150 kdyn, and 200 kdyn thoracic (T9) contusions from an Infinite Horizon impactor. ⋯ The DC EpoR/Epo immunoreactivities exhibited linear relationships with the behavioral correlates of post-lesional chronic pain development at DPO 42. SCI leads to long-lasting multicellular EpoR/Epo induction beyond the lesion core in the spinal cord regions that are involved in central pain development and regenerative processes. Our studies provide a time frame to investigate the effects of Epo application on motor function or pain development, especially in the later time course after lesioning.
-
Journal of neurotrauma · Feb 2018
Mithramycin A improves functional recovery by inhibiting BSCB disruption and hemorrhage after spinal cord injury.
After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption and progressive hemorrhage lead to secondary injury, subsequent apoptosis and/or necrosis of neurons and glia, causing permanent neurological deficits. Growing evidence indicates that mithramycin A (MA), an anti-cancer drug, has neuroprotective effects in ischemic brain injury and Huntington's disease (HD). However, the precise mechanism underlying its protective effects is largely unknown. ⋯ In addition, the expression of sulfonylurea receptor 1 (SUR1) and transient receptor potential melastatin 4 (TRPM4), which are known to mediate hemorrhage at an early stage after SCI, was significantly blocked by MA treatment. Finally, MA inhibited apoptotic cell death and improved functional recovery after injury. Thus, our results demonstrated that MA improves functional recovery by attenuating BSCB disruption and hemorrhage through the downregulation of SUR1/TRPM4 and MMP-9 after SCI.
-
Journal of neurotrauma · Feb 2018
Diaphragm and intercostal muscle activity following mid-cervical spinal cord contusion in the rat.
The present study was designed to investigate the diaphragm and intercostal muscle activity after unilateral mid-cervical spinal cord contusion in rats. Electromyogram (EMG) activity of the bilateral diaphragm and T2 intercostal muscle was measured in anesthetized and spontaneously breathing rats. Unilateral mid-cervical contusion caused an immediate reduction in inspiratory bursting in the bilateral diaphragm and intercostal muscles. ⋯ Notably, intercostal muscle activity was not substantially changed by mid-cervical spinal cord contusion from 3 days to 8 weeks post-contusion. These results suggest that mid-cervical spinal contusion induces a compensatory increase in contralateral diaphragmatic activity and greater utilization of a percentage of maximal inspiratory activity in the ipsilateral diaphragm. The maintenance of intercostal muscle activity may enable the animal to sustain essential breathing capacity after cervical spinal cord injury.
-
Journal of neurotrauma · Jan 2018
Randomized Controlled Trial Multicenter StudyCause and timing of death and sub-group differential effects of erythropoietin in the EPO-TBI study.
The EPO-TBI study randomized 606 patients with moderate or severe traumatic brain injury (TBI) to be treated with weekly epoetin alfa (EPO) or placebo. Six month mortality was lower in EPO treated patients in an analysis adjusting for TBI severity. Knowledge of possible differential effects by TBI injury subtype and acute neurosurgical treatment as well as timing and cause of death (COD) will facilitate the design of future interventional TBI trials. ⋯ However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to intensive care unit (ICU) admission (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.14-0.61, p = 0.001, p for interaction = 0.003) and in this subgroup, fewer patients died of cerebral causes in the EPO than in the placebo group (5% compared with 14%, p = 0.03). In conclusion, most TBI deaths were from cerebral causes that occurred during the first 2 weeks, and were related to withdrawal of care. EPO appeared to specifically reduce cerebral deaths in the important subgroup of patients with a diffuse type of injury not requiring a neurosurgical intervention prior to randomization.
-
Journal of neurotrauma · Jan 2018
Transcranial Doppler Systolic Flow Index and ICP Derived Cerebrovascular Reactivity Indices in TBI.
The purpose of our study was to explore relationships between transcranial Doppler (TCD) indices of cerebrovascular reactivity and those derived from intracranial pressure (ICP). Goals included: A) confirming previously described co-variance patterns of TCD/ICP indices, and B) describing thresholds for systolic flow index (Sx; correlation between systolic flow velocity [FVs] and cerebral perfusion pressure [CPP]) associated with outcome. In a retrospective cohort of traumatic brain injury (TBI) patients: with TCD and ICP monitoring, we calculated various continuous indices of cerebrovascular reactivity: A) ICP (pressure reactivity index [PRx]: correlation between ICP and mean arterial pressure [MAP]; PAx: correlation between pulse amplitude of ICP [AMP] and MAP; RAC: correlation between AMP and CPP) and B) TCD (mean flow index [Mx]: correlation between mean flow velocity [FVm] and CPP; Mx_a: correlation between FVm and MAP; Sx: correlation between FVs and CPP; Sx_a: correlation between FVs and MAP; Dx: correlation between diastolic flow velocity [FVd] and CPP; Dx_a: correlation between FVd and MAP). ⋯ TCD systolic indices are most closely associated with ICP indices. Sx and Sx_a likely provide better approximation of ICP indices, compared with Mx/Mx_a/Dx/Dx_a. Sx provides superior outcome prediction, versus Mx, with defined thresholds.