Induction of Monocarboxylate Transporter 2 Expression and Ketone Transport following Traumatic Brain Injury in Juvenile and Adult Rats

Object. The authors tested the hypothesis that intracranial bone marrow (BM) transplantation after traumatic brain injury (TBI) in rats provides therapeutic benefit. Methods. Sixty-six adult Wistar rats, weighing 275 to 350 g each, were used for the experiment. Bone marrow prelabeled with bromodeoxyuridine (BrdU) was harvested from tibias and femurs of healthy adult rats. Other animals were subjected to controlled cortical impact, and BM was injected adjacent to the contusion 24 hours after the impact. The animals were killed at 4, 7, 14, or 28 days after transplantation. Motor function was evaluated both before and after the injury by using the rotarod test. After the animals had been killed, brain sections were examined using hemotoxylin and eosin and immunohistochemical staining methods. Histological examination revealed that, after transplantation, BM cells survived, proliferated, and migrated toward the injury site. Some of the BrdU-labeled BM cells were reactive, with astrocytic (glial fibrillary acid protein) and neuronal (NeuN and microtubule-associated protein) markers. Transplanted BM expressed proteins phenotypical of intrinsic brain cells, that is, neurons and astrocytes. A statistically significant improvement in motor function in rats that underwent BM transplantation, compared with control rats, was detected at 14 and 28 days posttransplantation. Conclusions. On the basis of their findings, the authors assert that BM transplantation improves neurological outcome and that BM cells survive and express nerve cell proteins after TBI.

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Upregulation of Interferon Regulatory Factor 6 Promotes Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats

Cellular and Molecular Neurobiology ◽

10.1007/s10571-015-0217-3 ◽

2015 ◽

Vol 36 (1) ◽

pp. 27-36 ◽

Cited By ~ 12

Author(s):

Yuchang Lin ◽

Dezhi Xu ◽

Xiaohong Li ◽

Chun Liu ◽

Xia Liu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Apoptosis ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Adult Rats ◽

Interferon Regulatory Factor 6

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The incidence of critical-illness-related-corticosteroid-insufficiency is associated with severity of traumatic brain injury in adult rats

Journal of the Neurological Sciences ◽

10.1016/j.jns.2014.04.032 ◽

2014 ◽

Vol 342 (1-2) ◽

pp. 93-100 ◽

Cited By ~ 12

Author(s):

Xin Chen ◽

Zilong Zhao ◽

Yan Chai ◽

Lanlan Luo ◽

Rongcai Jiang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Critical Illness ◽

Adult Rats ◽

Corticosteroid Insufficiency

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The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats

Experimental Neurology ◽

10.1016/j.expneurol.2010.03.026 ◽

2010 ◽

Vol 224 (1) ◽

pp. 241-251 ◽

Cited By ~ 21

Author(s):

Beverly S. Colley ◽

Linda L. Phillips ◽

Thomas M. Reeves

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Cyclosporin A ◽

Adult Rats ◽

Axonal Conduction

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Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats

10.1101/647420 ◽

2019 ◽

Author(s):

Solomon M. Adams ◽

Fanuel T. Hagos ◽

Jeffrey P. Cheng ◽

Robert S. B. Clark ◽

Patrick M. Kochanek ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mrna Expression ◽

Neurovascular Unit ◽

Post Injury ◽

Adult Rats ◽

Order Of Magnitude ◽

Liver And Kidney ◽

The Central Nervous System ◽

The Brain

ABSTRACTTraumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.Significance StatementBaseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.

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Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats

Neuroscience Insights ◽

10.1177/2633105520968904 ◽

2020 ◽

Vol 15 ◽

pp. 263310552096890

Author(s):

Son T Ton ◽

Natalie S Adamczyk ◽

Jack P Gerling ◽

Ian C Vaagenes ◽

Joanna Y Wu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Dentate Gyrus ◽

Proliferative Response ◽

Male Rats ◽

Public Health Issue ◽

Adult Rats ◽

Double Labeling ◽

Post Traumatic

Background: Traumatic brain injury is a significant public health issue that results in serious disability in survivors. Traumatic brain injury patients are often intoxicated with alcohol when admitted to the hospital; however, it is not clear how acute intoxication affects recovery from a traumatic brain injury. Our group has previously shown that binge alcohol prior to traumatic brain injury resulted in long-term impairment in a fine sensorimotor task that was correlated with a decreased proliferative and neuroblast response from the subventricular zone. However, whether binge alcohol prior to traumatic brain injury affects the proliferative response in the hippocampal dentate gyrus is not yet known. Methods: Male rats underwent binge alcohol (3 g/kg/day) by gastric gavage for 3 days prior to traumatic brain injury. Cell proliferation was labeled by BrdU injections following traumatic brain injury. Stereological quantification and immunofluorescence confocal analysis of BrdU+ cells in the hippocampal dorsal dentate gyrus was performed at 24 hours, 1 week and 6 weeks post traumatic brain injury. Results: We found that either traumatic brain injury alone or binge alcohol alone significantly increased dentate gyrus proliferation at 24 hours and 1 week. However, a combined binge alcohol and traumatic brain injury regimen resulted in decreased dentate gyrus proliferation at 24 hours post-traumatic brain injury. At the 6 week time point, binge alcohol overall reduced the number of BrdU+ cells. Furthermore, more BrdU+ cells were found in the dentate hilar region of alcohol traumatic brain injury compared to vehicle traumatic brain injury groups. The location and double-labeling of these mismigrated BrdU+ cells was consistent with hilar ectopic granule cells. Conclusion: The results from this study showed that pre-traumatic brain injury binge alcohol impacts the injury-induced proliferative response in the dentate gyrus in the short-term and may affect the distribution of newly generated cells in the dentate gyrus in the long-term.

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