METHODS: In our study, we investigated the projections from the LPBn by performing stereotaxic injections of AAV2/2Retro-hSyn-EGFP (abbreviated as EGFP) into the bed nucleus of the stria terminalis (BNST) and AAV2/2Retro-hSyn-tdTomato (abbreviated as tdTomato) into the central amygdala (CeA) in mice. The animals subsequently underwent spared nerve injury (SNI) surgery on the contralateral side to the AAV injections. To examine the expression of calcitonin gene-related peptide (CGRP) and c-Fos, we conducted immunofluorescent histochemistry.
RESULTS: Our results indicated that approximately 26 % of the LPBn neurons retrogradely labeled with either EGFP or tdTomato were dual-labeled with both markers. Moreover, a significant majority (85.49 %) of these double-labeled neurons were CGRP positive (CGRP+). In mice subjected to SNI, nearly all of these neurons (93.25 %) were c-Fos positive (c-Fos+), indicating that they were activated.
CONCLUSION: These findings suggest that a subset of CGRP+ neurons in the LPBn projects to both the BNST and CeA via axon collaterals. Notably, under SNI conditions, these neurons may play a critical role in the transmission of chronic pain.
OBJECTIVE: The previous reports on the neuroprotective and GABAA receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.
METHODS: In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.
RESULTS: Administration of hispidulin (4, 10, and 50 mg/kg, i.p.) significantly reduced all three TGVS activation parameters induced by i.c. capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABAA receptor, furosemide (20 mg/kg, i.p.), did not significantly reverse the antimigraine effect of hispidulin.
CONCLUSION: To the best of our knowledge, this is the first report on hispidulin's suppressive effect on preclinical model of migraine. Further studies are required to explore the mechanism(s) of the antimigraine effect of hispidulin. However, these findings could potentially guide future clinical studies of hispidulin, with the aim of improving human health.
MATERIALS AND METHODS: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University (AKU), Karachi Pakistan. Electronic medical records of all in-patients including both genders and all age groups with documented COVID-19 from March to August 2020 were reviewed and recorded on a pre-structured performa. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. Between-group differences were tested using the Chi-square and Mann-Whitney's U-test. The receiver operating characteristic curve was plotted for serum PCT with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analysed using SPSS.
RESULTS: 336 patients were reviewed as declared COVID-19 positive during the study duration, and 136 were included in the final analysis including 101 males and 35 females. A statistically significant difference in PCT was found between severe and non-severe COVID-19 (p value=0.01); and survivors and nonsurvivors (p value<0.0001). PCT, older age and increased duration of hospital stay were revealed as variables independently associated with mortality. On ROC analysis, an AUC of 0.76 for mortality prediction was generated for PCT.
CONCLUSION: Baseline serum PCT concentration is a promising predictor of mortality and severity in COVID-19 cases when considered in combination with clinical details and other laboratory tests.