Thrombin is a Na⁺-activated allosteric serine protease of the chymotrypsin family involved in coagulation, inflammation, cell protection, and apoptosis. Increasingly, the role of thrombin in the brain has been explored. Low concentrations of thrombin are neuroprotective, while high concentrations exert pathological effects. However, greater attention regarding the involvement of thrombin in normal and pathological processes in the central nervous system is warranted. In this review, we explore the mechanisms of thrombin action, localization, and functions in the central nervous system and describe the involvement of thrombin in stroke and intracerebral hemorrhage, neurodegenerative diseases, epilepsy, traumatic brain injury, and primary central nervous system tumors. We aim to comprehensively characterize the role of thrombin in neurological disease and injury.

Traumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.

Introduction: Individuals recovering from acute COVID‐19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long‐COVID. Long‐term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post‐COVID‐19 syndrome.Objectives: This systematic review and meta‐analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID‐19 and to identify their associated functional consequences and inflammatory correlates.Methods: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory‐confirmed COVID‐19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes.Results: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co‐outcomes. Proportional meta‐analyses of pooled logit‐transformed values of single proportions were performed using the random‐effects‐restricted maximum‐likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system‐related pain symptoms, respectively, for up to one year after acute phase resolution of COVID‐19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality‐of‐life impairments and some inflammatory biomarker elevations were associated with the persistence of long‐COVID pain symptoms.Conclusion: This study's findings suggest that although not well characterized, long‐COVID pain symptoms are being experienced by non‐negligible proportions of those recovering from acute COVID‐19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.

Traumatic brain injury (TBI) is considered the most common neurological disorder among people under the age of 50. In modern combat zones, a combination of TBI and organophosphates (OP) can cause both fatal and long-term effects on the brain. We utilized a mouse closed-head TBI model induced by a weight drop device, along with OP exposure to paraoxon. Spatial and visual memory as well as neuron loss and reactive astrocytosis were measured 30 days after exposure to mild TBI (mTBI) and/or paraoxon. Molecular and cellular changes were assessed in the temporal cortex and hippocampus. Cognitive and behavioral deficits were most pronounced in animals that received a combination of paraoxon exposure and mTBI, suggesting an additive effect of the insults. Neuron survival was reduced in proximity to the injury site after exposure to paraoxon with or without mTBI, whereas in the dentate gyrus hilus, cell survival was only reduced in mice exposed to paraoxon prior to sustaining a mTBI. Neuroinflammation was increased in the dentate gyrus in all groups exposed to mTBI and/or to paraoxon. Astrocyte morphology was significantly changed in mice exposed to paraoxon prior to sustaining an mTBI. These results provide further support for assumptions concerning the effects of OP exposure following the Gulf War. This study reveals additional insights into the potentially additive effects of OP exposure and mTBI, which may result in more severe brain damage on the modern battlefield.

Background: Traumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed a ketogenic diet (KD) perform better in learning tasks than those fed a standard diet (SD) following brain injury. The goal of this study was to examine whether KD is neuroprotective in a TBI mouse model. Methods: We utilized a closed head injury model to induce mild TBI (mTBI) in mice. Mice were fed KD or SD starting immediately following the trauma and throughout the following 30 days. Tail blood ketone bodies levels were checked at 0, 3, 7 and 30 days post injury. Behavioral tests took place at 7 and 30days post injury, visual and spatial memory impairments were assessed using the Novel object recognition (NOR) paradigm and the Y-maze test, respectively, and anxiety-like behavior was assessed using the elevated plus maze test. Primary mouse SIRT1 levels antibodies were used to detect changes in protein levels following TBI induction and treatments 7 and 30 days post injury and Immunohistochemical sections were stained with, NeuN (for mature neurons), Iba-1 (for microglia) and GFAP (for astrocyte). Results: Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y‑maze and NOR tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced microglia activation and astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. Conclusion: These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating mTBI.