清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Evidence of Progressive Brainstem Pathology after Repeated Seizure Exposure in a Novel Rat Model of SUDEP

脑干 癫痫 医学 心肺适能 内科学 发作性 麻醉 内分泌学 病理 神经科学 心理学 精神科
作者
Anna D. Manis,Denise R. Cook-Snyder,Erin Lindsey Duffy,Alexander Staruschenko,Matthew R. Hodges
出处
期刊:The FASEB Journal [Wiley]
卷期号:34 (S1): 1-1
标识
DOI:10.1096/fasebj.2020.34.s1.04175
摘要

Mutations in ion channel genes can alter neuronal excitability and have been linked to seizure disorders in humans. We previously established that a knockout rat model of Kcnj16, which encodes potassium channel subunit Kir5.1, on a Dahl SS background (SSKcnj16−/−) exhibits renal and respiratory impairments, in addition to audiogenic reflex epilepsy. While seizures can be considered benign acute events, patients with uncontrolled epilepsy are at high risk for Sudden Unexplained Death in Epilepsy (SUDEP), predicted to be due to cardiorespiratory failure following repeated seizures. The SSKcnj16−/− rat allows intractable epilepsy to be modeled with modifiable SUDEP risk by regulating seizure number and providing a controlled experimental environment with consistent occurrence of seizure-induced death. During daily seizure exposure for up to 10 days, we observed progressive exacerbation of post-ictal respiratory rate and heart rate suppression with spontaneous mortality in 33% of SSKcnj16−/− rats within hours of a seizure. We tested the hypothesis that repeated seizures induces neuroinflammation and dysregulation of adenosine (ADO) and serotonin (5HT) within brainstem cardiorespiratory nuclei, which may contribute to progressive cardiorespiratory suppression and subsequent mortalities in SSkcnj16−/− rats. Quantification of brainstem neurochemicals by HPLC revealed increased ADO and decreased 5HT in seizure-exposed compared to naïve SSkcnj16−/− rats. These findings appeared to be brainstem-specific as ADO levels in the cortex of seizure exposed rats were decreased. Western blot analyses of whole brainstem lysates showed trends toward decreased expression of ADO kinase (ADK) and A1 receptor (A1R) in seizure-exposed rats. We used immunofluorescent staining and confocal imaging to label and quantify total 5HT, serotonergic neurons (tryptophan hydroxylase, TPH), microglia (Iba1), astrocytes (GFAP), total neurons (NeuN), and total nuclei (DAPI) in respiratory brainstem nuclei of SSkcnj16−/− rats exposed to 0, 3, or 10 seizures (n=2/group). Consistent with our HPLC data, 5HT staining was decreased in the pre-Bötzinger Complex (preBötC), Nucleus Ambiguus (NA) and medullary Raphe (MR) of seizure-exposed rats, which also showed fewer TPH-positive neurons in MR. Staining also revealed that seizures may induce brainstem inflammation that resulted in transient increases reactive microglia and progressive astrogliosis in these rats. SSkcnj16−/− rats showed increased Iba1 after 3 seizures but no change after 10 seizures in the preBötC, NA, MR and nucleus of the solitary tract (NTS). GFAP progressively increased after 3 and 10 seizures in preBötC, NTS, and MR. Further studies will focus on validating these finding by increasing the number of animals in experimental groups and evaluating additional inflammatory markers. This preliminary data suggests that dysregulation of ADO and 5HT and/or inflammation in respiratory brainstem nuclei may mediate respiratory suppression and subsequent mortality associated with repeated seizure exposure in SSKcnj16−/− rats, which may have central relevance to the pathophysiology of SUDEP which remains poorly understood. Support or Funding Information R01 HL122358

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
科研通AI2S应助cc采纳,获得10
1秒前
王洋洋完成签到 ,获得积分10
6秒前
zzf关闭了zzf文献求助
13秒前
JamesPei应助ceeray23采纳,获得30
13秒前
cc完成签到,获得积分10
15秒前
宝贝完成签到 ,获得积分10
44秒前
科目三应助dingding采纳,获得10
46秒前
59秒前
研友_Y59785应助常有李采纳,获得10
1分钟前
zhdjj完成签到 ,获得积分10
1分钟前
CC发布了新的文献求助10
1分钟前
Davidjin完成签到,获得积分10
1分钟前
平常的三问完成签到 ,获得积分10
1分钟前
natsu401完成签到 ,获得积分10
1分钟前
我睡觉的时候不困完成签到 ,获得积分10
1分钟前
perfect完成签到 ,获得积分10
2分钟前
星辰大海应助常有李采纳,获得20
2分钟前
2分钟前
神勇的天问完成签到 ,获得积分10
2分钟前
阿狸完成签到 ,获得积分10
2分钟前
ceeray23发布了新的文献求助30
2分钟前
喜悦的鬼神完成签到 ,获得积分10
2分钟前
水晶李完成签到 ,获得积分10
2分钟前
清脆钧关注了科研通微信公众号
3分钟前
Destiny完成签到,获得积分10
3分钟前
仙女完成签到 ,获得积分10
3分钟前
南风完成签到,获得积分10
3分钟前
常有李完成签到,获得积分10
3分钟前
秋思冬念完成签到 ,获得积分10
3分钟前
南北完成签到 ,获得积分10
3分钟前
ceeray23发布了新的文献求助20
3分钟前
畅快的刚完成签到,获得积分10
3分钟前
文献蚂蚁完成签到,获得积分10
3分钟前
BMG完成签到,获得积分10
3分钟前
朝夕之晖完成签到,获得积分10
3分钟前
CGBIO完成签到,获得积分10
3分钟前
zzf完成签到,获得积分10
3分钟前
冷傲半邪完成签到,获得积分10
4分钟前
4分钟前
曾经不言完成签到 ,获得积分10
4分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990732
求助须知:如何正确求助?哪些是违规求助? 3532220
关于积分的说明 11256570
捐赠科研通 3271081
什么是DOI,文献DOI怎么找? 1805229
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234