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- Lendvai-Emmert, Dominika, et al.
(författare)
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Mild traumatic brain injury-induced persistent blood-brain barrier disruption is prevented by cyclosporine A treatment in hypertension
- 2023
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Mild traumatic brain injury (mTBI) and hypertension synergize to induce persistent disruption of the blood-brain barrier (BBB), neuroinflammation and cognitive decline. However, the underlying mechanisms are not known. Cerebral production of Cyclophilin A (CyPA) is induced in hypertension and after TBI, and it was demonstrated to activate the nuclear factor-κB (NF-kB)- matrix-metalloproteinase-9 (MMP-9) pathway in cerebral vessels leading to BBB disruption.METHODS: To test the role of CyPA in mTBI- and hypertension-induced BBB disruption we induced mTBI in normotensive and spontaneously hypertensive rats (SHR), then the animals were treated with cyclosporine A (a specific inhibitor of CyPA production) or vehicle for 7 days. We assessed BBB permeability and integrity, cerebral expression and activity of the CyPA-NF-kB-MMP-9 pathway, extravasation of fibrin and neuroinflammation.RESULTS: We found that mild TBI induced BBB disruption and upregulation of the CyPA-NF-kB-MMP-9 pathway in hypertension, which were prevented by blocking CyPA. Cyclosporine treatment and preservation of BBB function prevented accumulation of blood-derived fibrin in the brain parenchyma of hypertensive rats after mTBI and reversed increased neuroinflammation.DISCUSSION: We propose that mTBI and hypertension interact to promote BBB disruption via the CyPA-NF-kB-MMP-9 pathway, and inhibition of cyclophilin production after mTBI may exert neuroprotection and improve cognitive function in hypertensive patients.
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| 2. |
- Magyar-Sumegi, Zsofia Dina, et al.
(författare)
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Acute neuroendocrine changes after traumatic brain injury
- 2024
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Ingår i: Brain & spine. - : Elsevier. - 2772-5294. ; 4
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Post-traumatic hypopituitarism (PTHP) is a significant, but often neglected consequence of traumatic brain injury (TBI).RESEARCH QUESTION: We aimed to provide a comprehensive overview of epidemiology, pathophysiology, clinical features and diagnostic approaches of PTHP.MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Library and Web of Science were searched. 45 articles of human studies evaluating acute endocrine changes following mild, moderate and severe TBI were selected.RESULTS: Severity of TBI seems to be the most important risk factor of PTHP. Adrenal insufficiency (AI) was present in 10% of TBI patients (prevalence can be as high as 50% after severe TBI), and hypocortisolemia is a predictor of mortality and long-term hypopituitarism. Suppression of the thyroid axis in 2-33% of TBI patients may be an independent predictor of adverse neurological outcome, as well. 9-36% of patients with severe TBI exhibit decreased function of the somatotrophic axis with a divergent effect on the central nervous system. Arginine-Vasopressin (AVP) deficiency is present in 15-51% of patients, associated with increased mortality and unfavorable outcome. Due to shear and injury of the stalk hyperprolactinemia is relatively common (2-50%), but it bears little clinical significance. Sex hormone levels remain within normal values.DISCUSSION AND CONCLUSION: PTHP occurs frequently after TBI, affecting various axis and determining patients' outcome. However, evidence is scarce regarding exact epidemiology, diagnosis, and effective clinical application of hormone substitution. Future studies are needed to identify patients at-risk, determine the optimal timing for endocrine testing, and refine diagnostic and treatment approaches to improve outcome.
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