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AUTHOR
Christina Gölz
showing 8 related works from this author
Sex hormones modulate pathogenic processes in experimental traumatic brain injury.
2018
Clinical and animal studies have revealed sex-specific differences in histopathological and neurological outcome after traumatic brain injury (TBI). The impact of perioperative administration of sex steroid inhibitors on TBI is still elusive. Here, we subjected male and female C57Bl/6N mice to the controlled cortical impact (CCI) model of TBI and applied pharmacological inhibitors of steroid hormone synthesis, that is, letrozole (LET, inhibiting estradiol synthesis by aromatase) and finasteride (FIN, inhibiting dihydrotestosterone synthesis by 5α-reductase), respectively, starting 72 h prior CCI, and continuing for a further 48 h after CCI. Initial gene expression analyses showed that andro…
Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro–Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice*
2016
Objectives:The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. H
Administration of all‐ trans retinoic acid after experimental traumatic brain injury is brain protective
2020
BACKGROUND AND PURPOSE: All‐trans retinoic acid (ATRA) is a vitamin A metabolite, important in the developing and mature brain. Pre‐injury ATRA administration ameliorates ischaemic brain insults in rodents. This study examined the effects of post‐traumatic ATRA treatment in experimental traumatic brain injury (TBI). EXPERIMENTAL APPROACH: Male adult mice were subjected to the controlled cortical impact model of TBI or sham procedure and killed at 7 or 30 days post‐injury (dpi). ATRA (10 mg kg−1, i.p.) was given immediately after the injury and 1, 2 and 3 dpi. Neurological function and sensorimotor coordination were evaluated. Brains were processed for (immuno‐) histological, mRNA and protei…
RS1 (Rsc1A1) deficiency limits cerebral SGLT1 expression and delays brain damage after experimental traumatic brain injury
2018
Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that knockdown of Na+ -D-glucose cotransporter SGLT1 impaired outcome after middle cerebral artery occlusion and that widely expressed intracellular RS1 (RSC1A1) is involved in transcriptional and post-translational down-regulation of SGLT1. In the present study, we investigated whether SGLT1 is up-regulated during traumatic brain injury (TBI) and whether removal of RS1 in mice (RS1-KO) influences SGLT1 expression and outcome. Unexpectedly, brain SGLT1 mRNA in RS1-KO was similar to wild-type whereas it was increased in small intestine and decreased in kidney. One day after TBI, SGL…
Plasminogen activator inhibitor‐1 augments damage by impairing fibrinolysis after traumatic brain injury
2019
Objective Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. Methods We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation b…
Pharmacologic Inhibition of ADAM10 Attenuates Brain Tissue Loss, Axonal Injury and Pro-inflammatory Gene Expression Following Traumatic Brain Injury …
2021
The α-secretase A disintegrin and metalloprotease 10 (ADAM10) regulates various physiological and pathophysiological processes. Despite its broad functional implications during development, plasticity, and disease, no pharmacological approaches to inhibit ADAM10 in acute brain injury have been reported. Here, we examined the effects of the ADAM10 inhibitor GI254023X on the neurological and histopathological outcome after experimental traumatic brain injury (TBI). C57BL/6N mice were subjected to the controlled cortical impact (CCI) model of TBI or sham procedure and received GI254023X or vehicle during the acute phase of injury (n = 40, 100 mg/kg, 25% DMSO, 0.1 M Na2CO3, intraperitoneal, 30 …
Multifaceted Mechanisms of WY-14643 to Stabilize the Blood-Brain Barrier in a Model of Traumatic Brain Injury
2017
The blood-brain barrier (BBB) is damaged during ischemic insults such as traumatic brain injury or stroke. This contributes to vasogenic edema formation and deteriorate disease outcomes. Enormous efforts are pursued to understand underlying mechanisms of ischemic insults and develop novel therapeutic strategies. In the present study the effects of PPARα agonist WY-14643 were investigated to prevent BBB breakdown and reduce edema formation. WY-14643 inhibited barrier damage in a mouse BBB in vitro model of traumatic brain injury based on oxygen/glucose deprivation in a concentration dependent manner. This was linked to changes of the localization of tight junction proteins. Furthermore, WY-1…
Single intracerebroventricular progranulin injection adversely affects the blood–brain barrier in experimental traumatic brain injury
2021
Progranulin (PGRN) is a neurotrophic and anti-inflammatory factor with protective effects in animal models of ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury (TBI). Administration of recombinant (r) PGRN prevents exaggerated brain pathology after TBI in Grn-deficient mice, suggesting that local injection of recombinant progranulin (rPGRN) provides therapeutic benefit in the acute phase of TBI. To test this hypothesis, we subjected adult male C57Bl/6N mice to the controlled cortical impact model of TBI, administered a single dose of rPGRN intracerebroventricularly (ICV) shortly before the injury, and examined behavioral and biological effects up to 5 days post injury (dp…