Summary:Purpose: Early animal studies of the therapeutic mechanisms of vagus nerve stimulation (VNS) suggested that seizure suppression requires maximal activation of small, unmyelinated vagal C fibers. However, effective therapeutic stimulation parameters appear to be subthreshold for these fibers in humans, and there are no clinical reports of the autonomic side effects that would be expected if these fibers were maximally activated. We report here that selective destruction of C fibers with capsaicin does not affect VNS-induced seizure suppression in rats.Methods: Rats were pretreated with capsaicin or vehicle in three injections over a 2-day period. A cuff electrode was later implanted on the left cervical vagus nerve. Two days after surgery, VNS was given to half of the capsaicin-and vehicletreated rats. The remaining rats were connected to the stimulator but did not receive VNS. Thirty seconds after VNS onset, seizures were induced by pentylenetetrazol (PTZ), and seizure severity was measured. Two days later, the reciprocal VNS treatment was given, and PTZ-induced seizure severity was again measured.Results: VNS effectively reduced seizure severity in both capsaicin-and vehicle-treated rats as compared with their non-VNS baselines.Conclusions: These results indicate that activation of vagal C fibers is not necessary for VNS-induced seizure suppression. Key Words: VNS-Capsaicin-Fibers-Pentylenetetrazol-Anticonvulsant-Epilepsy.Vagus nerve stimulation (VNS) is a novel anticonvulsant therapy now gaining prominence for the treatment of refractory epilepsy. Compared with conventional epilepsy neurosurgery, this technique involves a lower-risk surgery and results in fewer complications (1). The surgery in humans involves the placement of spiral electrodes on the left cervical vagus nerve, with intermittent stimulation provided by a neurocybernetic prosthesis (NCP) (Cyberonics, Inc., Houston, TX, U.S.A.) implanted subcutaneously in the upper chest. Clinical trials have found the device to reduce the incidence of complex partial seizures in the majority of patients tested, with 20-40% of patients achieving a >50% reduction in seizure frequency (2). Stimulation parameters are adjusted to produce a minimum of side effects. Some side effects, such as a tingling sensation in the neck and temporary hoarseness during stimulation, do persist; however, significant gastrointestinal, cardiac, or respiratory effects are not apparent (2).At the cervical level, the afferent component of the vagus nerve is a composite of myelinated A and B fibers, and unmyelinated C fibers, conveying sensory information from a number of organs, including the heart, lungs, liver, stomach, and intestines. The afferent C fibers are the most numerous, accounting for ∼65-80% of the fibers in the cervical vagal trunk (3). Early animal studies on the therapeutic mechanisms of VNS suggested that seizure suppression requires the activation of vagal C fibers (4). However, effective therapeutic stimulation parameters appear to be subthreshold for vagal C f...

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Metabolism of living organisms can be disrupted by the changes in the environment and nutrient intake causing serious diseases such as sudden deaths in broilers. High environmental temperature and ad libitum feeding were suspected as predisposing factors inducing sudden deaths. Our objective was to determine the changes in serum enzyme levels and liver lesions in broiler birds subjected to high temperature and ad libitum feeding. COBB 500 broiler strain was (n=90) divided into three groups including control group (n=30) treatment 1 (n=30, 35 0 C for 12 h per day) and treatment 2 (n=30, fed ad libitum) and studied from 26 days to 40 days of age. Blood samples (1.5 ml) with 6 replications were withdrawn from wing vein of the birds. The serum Alkaline Phosphatase (ALP), Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Total Protein and Albumin levels were assessed using commercial kits. Liver tissues of 14, 20, 33 and 38 days old birds from treatment 3 (33 0 C, ad libitum feeding) were fixed, processed and stained with Haemotoxylin and Eosin for histopathological assessment. Data were analyzed using General Linear Model in Minitab 14. The ALP levels were increased with age in control group and treatment 1 group but decreased in the treatment 2 group. The ALT levels were decreased with age in control group and treatment 1, whereas, increased in the treatment 2 group. AST levels were increased in all three groups. The total Protein levels were increased in treatment 2 but Albumin levels were remained similar throughout the lifespan of birds. Histopathological studies revealed that hepatic necrosis was common in older birds.

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