Unexpected role of stress as a possible resilience mechanism upon mild traumatic brain injury (mTBI) in mice

Shavit‐Stein, Efrat; Gerasimov, A.; Aharoni, Shay Anat; Gofrit, Shany Guly; Pikus, Ellen; Pick, Chaim G.; Maggio, Nicola

doi:10.1016/j.mcn.2020.103586

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Other investigators have reported weight loss with similar weight drop models. Interestingly, this weight loss observation has been shown to be consistent over several models of experimental TBI including controlled cortical impact (CCI) [ 19 ], lateral and midline fluid percussion injury (FPI) [ 20 – 23 ], weight drop [ 24 – 26 ], and blast injury [ 27 , 28 ]. Most of the observations have been reported within the first 3 days post-injury but a couple of studies have shown longer lasting weight deficits (Lapinlampi et al, 2020; Moinard et al, 2005).…”

Section: Discussionmentioning

confidence: 70%

“…However, Leptin levels decrease after severe TBI [ 30 ], which does not explain increased weight loss with increasing injury severity. The weight data could be linked to acute stress caused by TBI [ 26 , 28 ]. We have seen weight loss associated with some of our more stressful behavioral tests and objective indicators of stress (e.g., corticosterone) seem to rise at the time of post-TBI weight loss [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

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Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

Graham,

Juzang,

White

2023

PLoS ONE

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To assess the long-term behavioral effects of repetitive mild traumatic brain injury (rmTBI), we employed a preclinical model of rmTBI and performed a battery of behavioral tests starting 14 weeks post-injury. Male Sprague-Dawley rats received four unilateral mild (6 m/s; 0.5 mm depth) controlled cortical impacts (CCI), centered 4 mm posterior and 3–4 mm lateral to the bregma, administered at five-day intervals. The animals’ weights were monitored throughout the study. We tested the rats for anxiety-like (elevated plus maze, open field test), depression-like (forced swim test), locomotor (rotarod, open field test), and spatial learning and memory (Morris water maze (MWM)) behavioral deficits. Overall, a mild behavioral phenotype was observed. Significant deficits were observed with the MWM, indicating that our injury model disrupts spatial learning and memory. An interesting aspect of these data is a directional/visual component to the spatial learning and memory deficits dependent on the zone in which the trial began. With the injury being unilateral, there may be an imbalance in visual acuity that contributes to the observed deficits. Analysis of weight gain data demonstrated that rmTBI reduces weight during the period while injuries are occurring. This may represent another measure that can be tracked to determine injury severity and recovery. RNA-seq analysis demonstrated that gene expression at the chronic endpoint could distinguish between the experimental groups even with a mild behavioral phenotype. Future studies would include a more severe injury paradigm to promote longer-lasting behavior changes.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

Graham,

Juzang,

White

2023

PLoS ONE

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The effect of Centella asiatica, cinnamon, and spirulina as neuroprotective based on histopathological findings in ratus Sprague Dawley with traumatic brain injury

Rosyidi,

Wardhana,

Priyanto

et al. 2024

Surgical Neurology International

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Background: Traumatic brain injury (TBI) is a global health problem with the potential to cause dangerous neurological problems. Based on histopathological findings in Sprague Dawley (SD) rats with TBI in the acute phase, the study seeks to discover the effect of Centella asiatica, cinnamon, and spirulina as neuroprotective. Methods: We conducted an experimental study with 30 SD rats randomly divided into three groups. The intervention was the administration of C. asiatica, cinnamon, and spirulina to the control and the experimental groups. Histological features were assessed using hematoxylin and eosin (H&E) staining and immunohistochemical examination. The data were analyzed using statistical analysis through correlation tests. Results: The test samples’ average body weights had P > 0.05, indicating no significant difference in the test sample body weights. Therefore, the variations in the expression level of the dependent variable were expected to be caused by the induction of brain injury and the administration of C. asiatica, cinnamon, and spirulina. In addition, the variables were not normally distributed. Thus, the Spearman test was carried out and showed the correlation was very strong, with a value of r = 0.818 and P < 0.05. Conclusion: Based on histopathological findings from the brains of SD rats with TBI, pegagan, cinnamon, and spirulina will protect the brain (neuroprotective) in the acute phase.

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PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy

Golderman

Goldberg

Gofrit

et al. 2023

IJMS

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Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.

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Unexpected role of stress as a possible resilience mechanism upon mild traumatic brain injury (mTBI) in mice

Cited by 4 publications

References 37 publications

Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

The effect of Centella asiatica, cinnamon, and spirulina as neuroprotective based on histopathological findings in ratus Sprague Dawley with traumatic brain injury

PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy

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