pregabalin and Brain-Injuries

Radiation-induced brain injury (RIBI) is the most serious complication of radiotherapy in patients with head and neck tumors, which seriously affects the quality of life. Currently, there is no effective treatment for patients with RIBI, and identifying new treatment that targets the pathological mechanisms of RIBI is urgently needed.. Immunofluorescence staining, western blotting, quantitative real-time polymerase chain reaction (Q-PCR), co-culture of primary neurons and microglia, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and CRISPR-Cas9-mediated gene editing techniques were employed to investigate the protective effects and underlying mechanisms of pregabalin that ameliorate microglial activation and neuronal injury in the RIBI mouse model.. Our findings showed that pregabalin effectively repressed microglial activation, thereby reducing neuronal damage in the RIBI mouse model. Pregabalin mitigated inflammatory responses by directly inhibiting cytoplasmic translocation of high-mobility group box 1 (HMGB1), a pivotal protein released by irradiated neurons which induced subsequent activation of microglia and inflammatory cytokine expression. Knocking out neuronal HMGB1 or microglial TLR2/TLR4/RAGE by CRISPR/Cas9 technique significantly inhibited radiation-induced NF-κB activation and pro-inflammatory transition of microglia.. Our findings indicate the protective mechanism of pregabalin in mitigating microglial activation and neuronal injury in RIBI. It also provides a therapeutic strategy by targeting HMGB1-TLR2/TLR4/RAGE signaling pathway in the microglia for the treatment of RIBI.

Topics: Animals; Brain Injuries; Cytokines; DNA Nucleotidylexotransferase; HMGB1 Protein; Mice; Microglia; Neurons; NF-kappa B; Pregabalin; Quality of Life; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4

In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats.. This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage.. All animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma+pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma+pregabalin groups.. The results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation.

Topics: Animals; Brain Injuries; Edema; Inflammation; Male; Pregabalin; Rats, Sprague-Dawley

To determine whether pregabalin produces long-term spasticity reduction in subjects previously identified as responding in short-term trials.. Prospective service evaluation of patients taking pregabalin for spasticity management for at least 1 year through a tertiary referral rehabilitation clinic. A graduated pregabalin withdrawal was undertaken as part of routine clinical management.. Twelve of 19 potential subjects agreed to participate. The primary outcome measures were visual analogue pain and spasticity scores at lowest dose of pregabalin compared to baseline and their choice to resume pregabalin therapy.. Mean pre-withdrawal pregabalin dosage was 386 mg/day, decreasing to 70 mg/day at mean lowest dosage. Median subjective spasticity scores increased from 4 at baseline to 6 at lowest dose (p < 0.01) without a significant increase in median pain scores. Two patients with epilepsy, whose other anti-convulsants were not altered, had seizures. Following the evaluation, five subjects chose to return to the original dose, five recommenced pregabalin at a lower dose and two subjects no longer required the drug.. Pregabalin withdrawal resulted in self-reports of increased spasticity without a concomitant increase in pain, with 91% choosing to continue pregabalin at the conclusion of the evaluation.

Topics: Analgesics; Anticonvulsants; Brain Injuries; Cerebral Palsy; Drug Administration Schedule; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Pain Measurement; Pregabalin; Prospective Studies; Spinal Cord Injuries; Treatment Outcome; Withholding Treatment

Topics: Adult; Anticonvulsants; Brain Injuries; Epilepsy; Erectile Dysfunction; gamma-Aminobutyric Acid; Humans; Male; Pregabalin