Evaluation of taurine neuroprotection in aged rats with traumatic brain injury

Gupte, Raeesa; Christian, Sarah K.; Keselman, Paul; Habiger, Joshua; Brooks, William M.; Harris, J. Ieuan

doi:10.1007/s11682-018-9865-5

Cited by 16 publications

(10 citation statements)

References 68 publications

(101 reference statements)

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“…Conversely, some neuroprotective strategies, such as the administration of taurine, an endogenous amino acid with antioxidant, anti-inflammatory and anti-apoptotic effects, and which is neuroprotective in adult TBI [ 221 ], is not effective following TBI in aged animals [ 219 ]. Moreover, nicotinamide, which improves functional outcome following young adult TBI [ 196 ], does not enhance functional recovery at low doses and even worsens functional deficit with higher doses [ 216 ].…”

Section: Post-traumatic Neuroinflammation and Its Consequences In Vivomentioning

confidence: 99%

“…Administration of anti-inflammatory or neuroprotective components, like nicotinamide, taurine or epothilone, revealed no effect or even worsened tissue loss and functional deficit in aged TBI mice [ 199 , 216 , 219 ]. Altogether, these studies illustrate the complexity of age-dependent mechanism of the consequences of TBI and the necessity to consider its singularity in treatments of aged populations.…”

Section: Post-traumatic Neuroinflammation and Its Consequences In Vivomentioning

confidence: 99%

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Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment

et al. 2021

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Traumatic brain injury (TBI) is a leading cause of death and disability all over the world. TBI leads to (1) an inflammatory response, (2) white matter injuries and (3) neurodegenerative pathologies in the long term. In humans, TBI occurs most often in children and adolescents or in the elderly, and it is well known that immune responses and the neuroregenerative capacities of the brain, among other factors, vary over a lifetime. Thus, age-at-injury can influence the consequences of TBI. Furthermore, age-at-injury also influences the pharmacological effects of drugs. However, the post-TBI inflammatory, neuronal and functional consequences have been mostly studied in experimental young adult animal models. The specificity and the mechanisms underlying the consequences of TBI and pharmacological responses are poorly understood in extreme ages. In this review, we detail the variations of these age-dependent inflammatory responses and consequences after TBI, from an experimental point of view. We investigate the evolution of microglial, astrocyte and other immune cells responses, and the consequences in terms of neuronal death and functional deficits in neonates, juvenile, adolescent and aged male animals, following a single TBI. We also describe the pharmacological responses to anti-inflammatory or neuroprotective agents, highlighting the need for an age-specific approach to the development of therapies of TBI.

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Section: Post-traumatic Neuroinflammation and Its Consequences In Vivomentioning

confidence: 99%

Section: Post-traumatic Neuroinflammation and Its Consequences In Vivomentioning

confidence: 99%

Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment

et al. 2021

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“…CCI and sham surgeries were carried out as we have previously described [26][27][28] . In brief, animals were anesthetized with isoflurane (4% induction, 2% maintenance in 2:1 Medical air:Oxygen).…”

Section: Controlled Cortical Impact (Cci) and Sham Surgeriesmentioning

confidence: 99%

“…All surgeries were carried out by a single surgeon, following methods previously reported [58][59][60] .…”

Section: Controlled Cortical Impact (Cci) and Sham Surgeriesmentioning

confidence: 99%

Comparing Imaging Biomarkers of Cerebral Edema after TBI in Young Adult Male and Female Rats

Minchew

Sk²,

Keselman

et al. 2021

Preprint

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Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 hours after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjects ex vivo. We found that in male rats, the injured cortex had higher brain water content and lower apparent diffusion coefficient (ADC) values compared with the contralateral side. Females did not show hemispheric differences for these measures. However, both males and females had similarly elevated T2 values in the injured cortex compared with the contralateral side. A strong correlation was observed between brain water content and T2 values in the injured cortex in male rats, but not in females. These findings raise questions about the clinical interpretation of radiological findings pertinent to edema in female TBI patients. A more mechanistic understanding of sex differences and similarities in TBI pathophysiology will help improve patient management and the development of effective treatment strategies for TBI in men and women.

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“…A recent study from our group showed that treatment with taurine, an anti-inflammatory, antioxidant, and anti-apoptotic therapy that had shown promise for TBI in young adult rats, did not show a similar degree of neuroprotection in elderly rats. 89 This highlights the likely influence of age on therapeutic efficacy and the critical need for inclusion of aged animal models in the drug development pipeline for TBI.…”

Section: Challenges To Modeling Tbi In Animalsmentioning

confidence: 99%

Models of Traumatic Brain Injury in Aged Animals: A Clinical Perspective

Iboaya

Harris

Arickx

et al. 2019

Neurorehabil Neural Repair

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States, with advanced age being one of the major predictors of poor prognosis. To replicate the mechanisms and multifaceted complexities of human TBI and develop prospective therapeutic treatments, various TBI animal models have been developed. These models have been essential in furthering our understanding of the pathophysiology and biochemical effects on brain mechanisms following TBI. Despite these advances, translating preclinical results to clinical application, particularly in elderly individuals, continues to be challenging. This review aims to provide a clinical perspective, identifying relevant variables currently not replicated in TBI animal models, to potentially improve translation to clinical practice, especially as it applies to elderly populations. As background for this clinical perspective, we reviewed articles indexed on PubMed from 1970 to 2019 that used aged animal models for studying TBI. These studies examined end points relevant for clinical translation, such as neurocognitive effects, sensorimotor behavior, physiological mechanisms, and efficacy of neuroprotective therapies. However, compared with the higher incidence of TBI in older individuals, animal studies on the basic science of aging and TBI remain remarkably scarce. Moreover, a fundamental disconnect remains between experiments in animal models of TBI and successful translation of findings for treating the older TBI population. In this article, we aim to provide a clinical perspective on the unique attributes of TBI in older individuals and a critical appraisal of the research to date on TBI in aged animal models as well as recommendations for future studies.

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Evaluation of taurine neuroprotection in aged rats with traumatic brain injury

Cited by 16 publications

References 68 publications

Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment

Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment

Comparing Imaging Biomarkers of Cerebral Edema after TBI in Young Adult Male and Female Rats

Models of Traumatic Brain Injury in Aged Animals: A Clinical Perspective

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