scholarly journals Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury

2012 ◽  
Vol 236 (2) ◽  
pp. 371-382 ◽  
Author(s):  
Kathleen M. Schoch ◽  
Heather N. Evans ◽  
Jennifer M. Brelsfoard ◽  
Sindhu K. Madathil ◽  
Jiro Takano ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Deficits

scholarly journals 3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 8276
Author(s):  
Pen-Sen Huang ◽  
Ping-Yen Tsai ◽  
Ling-Yu Yang ◽  
Daniela Lecca ◽  
Weiming Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Short Term Memory ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Cognitive Behaviors ◽  
Moderate Traumatic Brain Injury ◽  
Short And Long Term ◽  
Behavioral Impairments ◽  
Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

Guanosine Attenuates Behavioral Deficits After Traumatic Brain Injury by Modulation of Adenosinergic Receptors

2018 ◽  
Vol 56 (5) ◽  
pp. 3145-3158 ◽  
Author(s):  
Fernando Dobrachinski ◽  
Rogério R. Gerbatin ◽  
Gláubia Sartori ◽  
Ronaldo M. Golombieski ◽  
Alfredo Antoniazzi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Deficits

scholarly journals Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy

2018 ◽  
Vol 40 (2) ◽  
pp. 175-188 ◽  
Author(s):  
Michael J. Hylin ◽  
Ryan C. Holden ◽  
Aidan C. Smith ◽  
Aric F. Logsdon ◽  
Rabia Qaiser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Endoplasmic Reticulum ◽  
Brain Injury ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Short Term ◽  
Behavioral Deficits ◽  
Juvenile Rats ◽  
Tau Oligomers ◽  
Cci Model

The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso­ciated with the activation of a known tau kinase, glycogen synthase kinase-3β (GSK-3β), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury.

scholarly journals Mitochondria-Targeted Antioxidants as Potential Therapy for the Treatment of Traumatic Brain Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 124 ◽  
Author(s):  
Elena V. Stelmashook ◽  
Nickolay K. Isaev ◽  
Elisaveta E. Genrikhs ◽  
Svetlana V. Novikova
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Lesion ◽  
Lesion Volume ◽  
Negative Effects ◽  
Behavioral Deficits ◽  
Secondary Damage ◽  
Long Time ◽  
The Brain ◽  
Brain Water

The aim of this article is to review the publications describing the use of mitochondria-targeted antioxidant therapy after traumatic brain injury (TBI). Recent works demonstrated that mitochondria-targeted antioxidants are very effective in reducing the negative effects associated with the development of secondary damage caused by TBI. Using various animal models of TBI, mitochondria-targeted antioxidants were shown to prevent cardiolipin oxidation in the brain and neuronal death, as well as to markedly reduce behavioral deficits and cortical lesion volume, brain water content, and DNA damage. In the future, not only a more detailed study of the mechanisms of action of various types of such antioxidants needs to be conducted, but also their therapeutic values and toxicological properties are to be determined. Moreover, the optimal therapeutic effect needs to be achieved in the shortest time possible from the onset of damage to the nervous tissue, since secondary brain damage in humans can develop for a long time, days and even months, depending on the severity of the damage.

scholarly journals Increased Vulnerability of NFH-LacZ Transgenic Mouse to Traumatic Brain Injury-Induced Behavioral Deficits and Cortical Damage

1999 ◽  
Vol 19 (7) ◽  
pp. 762-770 ◽  
Author(s):  
Michio Nakamura ◽  
Kathryn E. Saatman ◽  
James E. Galvin ◽  
Uwe Scherbel ◽  
Ramesh Raghupathi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Dysfunction ◽  
Tissue Loss ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Beam Balance ◽  
Brain Injured ◽  
Neuromotor Function ◽  
Histopathologic Analysis

The authors evaluated the neurobehavioral and neuropathologic sequelae after traumatic brain injury (TBI) in transgenic (TG) mice expressing truncated high molecular weight neurofilament (NF) protein fused to beta-galactosidase (NFH-LacZ), which develop Lewy body-like NF-rich inclusions throughout the CNS. TG mice and their wild-type (WT) littermates were subjected to controlled cortical impact brain injury (TG, n=19; WT, n=17) or served as uninjured controls (TG, n =11; WT, n =11). During a 3-week period, mice were evaluated with an array of neuromotor function tests including neuroscore, beam balance, and both fast and slow acceleration rotarod. Brain-injured WT and TG mice showed significant motor dysfunction until 15 days and 21 days post-injury, respectively ( P < .025). Compared with brain-injured WT mice, brain-injured TG mice had significantly greater motor dysfunction as assessed by neuroscore ( P < .01) up to and including 15 days post-injury. Similarly, brain-injured TG mice performed significantly worse than brain-injured WT mice on slow acceleration rotarod at 2, 8, and 15 days post-injury ( P < .05), and beam balance over 2 weeks post-injury ( P < .01). Histopathologic analysis showed significantly greater tissue loss in the injured hemisphere in TG mice at 4 weeks post-injury ( P < .01). Together these data show that NFH-LacZ TG mice are more behaviorally and histologically vulnerable to TBI than WT mice, suggesting that the presence of NF-rich inclusions may exacerbate neuromotor dysfunction and cell death after TBI.

scholarly journals Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats

2018 ◽  
Vol 22 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Rachel K. Rowe ◽  
Jordan L. Harrison ◽  
Timothy W. Ellis ◽  
P. David Adelson ◽  
Jonathan Lifshitz
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Late Onset ◽  
Human Condition ◽  
Acute Injury ◽  
Behavioral Deficits ◽  
Fluid Percussion ◽  
Skull Size ◽  
Righting Reflex ◽  
Old Rats

OBJECTIVEExperimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology. In this study, the authors sought to adapt a midline FPI to postnatal day (PND) 17 and 35 rats. The authors hypothesized that scaling the craniectomy size based on skull dimensions would result in a reproducible injury comparable to the standard midline FPI in adult rats.METHODSPND17 and PND35 rat skulls were measured, and trephines were scaled based on skull size. Custom trephines were made. Rats arrived on PND10 and were randomly assigned to one of 3 cohorts: PND17, PND35, and 2 months old. Rats were subjected to midline FPI, and the acute injury was characterized. The right reflex was recorded, injury-induced apnea was measured, injury-induced seizure was noted, and the brains were immediately examined for hematoma.RESULTSThe authors’ hypothesis was supported; scaling the trephines based on skull size led to a reproducible injury in the PND17 and PND35 rats that was comparable to the injury in a standard 2-month-old adult rat. The midline FPI suppressed the righting reflex in both the PND17 and PND35 rats. The injury induced apnea in PND17 rats that lasted significantly longer than that in PND35 and 2-month-old rats. The injury also induced seizures in 73% of PND17 rats compared with 9% of PND35 rats and 0% of 2-month-old rats. There was also a significant relationship between the righting reflex time and presence of seizure. Both PND17 and PND35 rats had visible hematomas with an intact dura, indicative of diffuse injury comparable to the injury observed in 2-month-old rats.CONCLUSIONSWith these procedures, it becomes possible to generate brain-injured juvenile rats (pediatric [PND17] and adolescent [PND35]) for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented.

scholarly journals Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

2017 ◽  
Vol 11 (1) ◽  
pp. dmm030387 ◽  
Author(s):  
Guoxiang Wang ◽  
Yi Ping Zhang ◽  
Zhongwen Gao ◽  
Lisa B. E. Shields ◽  
Fang Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rotational Acceleration ◽  
Behavioral Deficits ◽  
Developing Mice

scholarly journals Zinc and Traumatic Brain Injury: From Chelation to Supplementation

2020 ◽  
Vol 8 (3) ◽  
pp. 36 ◽  
Author(s):  
Cathy W. Levenson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Incidence Rate ◽  
Molecular Mechanisms ◽  
Behavioral Deficits ◽  
Zinc Accumulation ◽  
Regulated Gene Expression

With a worldwide incidence rate of almost 70 million annually, traumatic brain injury (TBI) is a frequent cause of both disability and death. Our modern understanding of the zinc-regulated neurochemical, cellular, and molecular mechanisms associated with TBI is the result of a continuum of research spanning more than three decades. This review describes the evolution of the field beginning with the initial landmark work on the toxicity of excess neuronal zinc accumulation after injury. It further shows how the field has expanded and shifted to include examination of the cellular pools of zinc after TBI, identification of the role of zinc in TBI-regulated gene expression and neurogenesis, and the use of zinc to prevent cognitive and behavioral deficits associated with brain injury.

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