ABSTRACT
@#Objectives: Calcitonin gene-related peptide (CGRP) is currently considered to be a major contributing factor in migraine headache. Botulinum toxin type A (BTXA) was found to be effective in migraine prevention. However, the mechanism of action in patients was unknown. Using injection as in clinical setting, the study aimed to determine whether BTXA could decrease the sensitization of the trigeminovascular nociceptive system through the reduction of CGRP action. Methods: Adult male Wistar rats were pretreated with normal saline solution or BTXA before KCl application to induce cortical spreading depression (CSD) or NaCl application as a control. Regional cerebral blood flow at parietal cortex was measured for 90 min after KCl or NaCl application. Tissues from trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were then collected for CGRP and c-Fos measurement respectively. Results: BTXA pretreatment significantly decreased the cumulative blood flow and number of hyperemic peaks induced by KCl. Numbers of CGRP positive cells at TG and c-Fos positive cells at TNC were also reduced by BTXA.Conclusion: BTXA pretreatment reduced CGRP production and release from the TG leading to lessen CSD production and persistent activation of TNC which played a major role in migraine headache.
ABSTRACT
Background: Deficiency of vitamin C (L-ascorbic acid; AA) may induce renal glomular dysfunction in diabetes. Few data are available for the role of continuous upplementation of AA on glomerular dysfunction and pathologyinduced during diabetes. Objective: To investigate long-term effects of AA supplementation on glomerular changes in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced in Sprague-Dawley rats (180-220 g) by injection of STZ (55 mg/kg bw, iv). The rats were divided into controls (CON), AA-supplemented controls (CON-AA), diabetic (STZ) and AA-supplemented diabetic rats (STZ-AA). AA (1 g/L) was continuously supplemented to the rats for 4, 8, 16 and 24 weeks. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR) malondialdehyde (MDA) and transforming growth factor-β1 (TGF-β1) levels were measured in the renal cortex. Glomerular morphology was examined histologically. Renal hypertrophic index was calculated using kidney-to-body weight ratio (KW/BW). Results: Decreases in GFR and ERPF were ameliorated at week 16 and deteriorated at week 24 after AA supplementation in STZ-AA rats. High blood glucose concentration was attenuated only at week 16. MAD and TGF-β1 levels in renal cortex decreased significantly in STZ-AA rats at week 16 but not at week 24. The number of abnormal glomeruli and KW/BW decreased significantly at week 16 in STZ-AA rats. Conclusion: Long-term supplementation of AA may ameliorate the glomerular changes induced by diabetes.