Journal of neurotrauma
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Journal of neurotrauma · Sep 2011
Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury.
A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). ⋯ Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells.
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Journal of neurotrauma · Sep 2011
Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury.
Previous studies have shown that the change of cerebral metabolic rate of glucose (CMRglc) in response to traumatic brain injury (TBI) is different in young (PND35) and adult rats (PND70), and that prolonged ketogenic diet treatment results in histological and behavioral neuroprotection only in younger rat brains. However, the mechanism(s) through which ketones act in the injured brain and the biochemical markers of their action remain unknown. Therefore, the current study was initiated to: 1) determine the effect of injury on the neurochemical profile in PND35 compared to PND70 rats; and 2) test the effect of early post-injury administration of ketogenic diet on brain metabolism in PND35 versus PND70 rats. ⋯ The improvement in energy metabolism in the PND35 brains was accompanied by the recovery of NAA and reduction of lactate levels, as well as amelioration of the deficits of other amino acids and membrane metabolites. These results indicate that the PND35 brains are more resistant to the injury, indicated by a delayed deficit in energy metabolism. Moreover, the younger brains revert to ketones metabolism more quickly than do the adult brains, resulting in better neurochemical and cerebral metabolic recovery after injury.
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Journal of neurotrauma · Sep 2011
Structured assessment of hypopituitarism after traumatic brain injury and aneurysmal subarachnoid hemorrhage in 1242 patients: the German interdisciplinary database.
Clinical studies have demonstrated that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. This study aimed to assess the prevalence and associated factors of post-traumatic hypopituitarism in a large national registry of patients with TBI and SAH. Data were collected from 14 centers in Germany and Austria treating patients for TBI or SAH and performing endocrine assessments. ⋯ TBI patients with abnormal stimulation tests had suffered from more severe TBI than patients with normal stimulation tests. In conclusion, our data confirm that hypopituitarism is a common complication of TBI and SAH. It is possible that patients with a higher likelihood of hypopituitarism were selected for endocrine stimulation tests.
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Journal of neurotrauma · Sep 2011
Mild stretch-induced injury increases susceptibility to interleukin-1β-induced release of matrix metalloproteinase-9 from astrocytes.
Traumatic brain injury (TBI) results in the activation of glia and the release of proinflammatory cytokines, including interleukin (IL)-1β. The response of astrocytes to mild TBI has not been well studied. We used an in vitro model of cell stretch to investigate the effects of mild mechanical insult on astrocyte injury (lactate dehydrogenase and propidium iodide), and on mediators of inflammation including IL-1β, the chemokine CX3CL1, and nitrite. ⋯ In contrast, the combination of mild stretch followed by IL-1β resulted in greater activation of the ERK pathway compared to either stimulus alone, and also resulted in an increase in the production of MMP-9 by astrocytes. Inhibition of the ERK pathway suppressed the increase in MMP-9 induced by the combination of stretch and IL-1β treatment. These results suggest that a primary mild mechanical injury renders astrocytes more susceptible to a secondary exposure to a proinflammatory cytokine such as IL-1β via the activation of the ERK pathway, and suggest a mechanism by which a mild head injury may confer increased susceptibility to neurologic injury caused by a subsequent insult.
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Journal of neurotrauma · Sep 2011
Correlation of MR diffusion tensor imaging parameters with ASIA motor scores in hemorrhagic and nonhemorrhagic acute spinal cord injury.
This study investigated correlations between American Spinal Injury Association (ASIA) clinical injury motor scores in patients with traumatic cervical cord injury and magnetic resonance (MR) diffusion tensor imaging (DTI) parameters. Conventional imaging and DTI were performed to evaluate 25 patients (age, 39.7±13.9 years; 4 women, 21 men) with blunt spinal cord injury and 11 volunteers (age, 31.5±10.7 years; 3 women, 8 men). Cord contusions were hemorrhagic (HC) in 13 and non-hemorrhagic (NHC) in 12 patients. ⋯ Within the NHC group, strong correlations were observed between ASIA motor scores and average MD, FA, λ(⊥), and λ(‖) at the injury site. However, no correlation was observed within the HC group between any of the DTI parameters and ASIA motor scores. DTI parameters reflect the severity of spinal cord injury and correlate well with ASIA motor scores in patients with NHC.