Dysfunction and Death of Neurons in Human Degenerative Neurological Diseases and in Animal Models

2007 ◽  
pp. 30-48 ◽  
Author(s):  
Donald L. Price ◽  
Linda C. Cork ◽  
Robert G. Struble ◽  
Cheryl A. Kitt ◽  
Lary C. Walker ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurological Diseases

Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: implication for pharmacological interventions

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Mehdi Ghasemi ◽  
Arash Hadipour-Niktarash
Keyword(s):  
Animal Models ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neurological Diseases ◽  
Juvenile Myoclonic Epilepsy ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Pharmacological Interventions ◽  
Nicotinic Acetylcholine ◽  
Neuronal Nachr

AbstractAccumulating evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) may play a key role in the pathophysiology of some neurological diseases such as epilepsy. Based on genetic studies in patients with epileptic disorders worldwide and animal models of seizure, it has been demonstrated that nAChR activity is altered in some specific types of epilepsy, including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and juvenile myoclonic epilepsy (JME). Neuronal nAChR antagonists also have antiepileptic effects in pre-clinical studies. There is some evidence that conventional antiepileptic drugs may affect neuronal nAChR function. In this review, we re-examine the evidence for the involvement of nAChRs in the pathophysiology of some epileptic disorders, especially ADNFLE and JME, and provide an overview of nAChR antagonists that have been evaluated in animal models of seizure.

scholarly journals Changes in Physiological and Pathological Behaviours Produced by Deep Microelectrode Implantation Surgery in Rats: A Temporal Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Gustavo A. Chiprés-Tinajero ◽  
Miguel A. Núñez-Ochoa ◽  
Laura Medina-Ceja
Keyword(s):  
Animal Models ◽  
Neurological Diseases ◽  
Behavioural Change ◽  
Temporal Analysis ◽  
Exploratory Activity ◽  
Male Wistar Rats ◽  
Experimental Protocols ◽  
Convulsive Seizures ◽  
The Impact ◽  
Mean Time

Physiological behaviours such as the sleep-wake cycle and exploratory behaviours are important parameters in intact and sham-operated animals and are usually thought to be unaffected by experimental protocols in which neurosurgery is performed. However, there is insufficient evidence in the literature on the behavioural and cognitive effects observed after deep microelectrode implantation surgery in animal models of neurological diseases. Similarly, in studies that utilize animal models of neurological diseases, the impact of surgery on the pathological phenomena being studied is often minimized. Based on these considerations, we performed a temporal analysis of the effects of deep microelectrode implantation surgery in the hippocampus of rats on quiet wakefulness, sleep, and exploratory activity and the pathological behaviours such as convulsive seizures according to the Racine scale. Male Wistar rats (210-300 g) were used and grouped in sham and epileptic animals. Single doses of pilocarpine hydrochloride (2.4 mg/2 μl; i.c.v.) were administered to the animals to generate spontaneous and recurrent seizures. Deep microelectrode implantation surgeries in both groups and analysis of Fast ripples were performed. Physiological and pathological behaviours were recorded through direct video monitoring of animals (24/7). Our principal findings showed that in epileptic animals, one of the main behaviours affected by surgery is sleep; as a consequence of this behavioural change, a decrease in exploratory activity was also found as well as the mean time spent daily in seizures of scale 4 and the number of seizure events of scales 4 and 5 was increased after surgery. No significant correlations between the occurrence of FR and seizure events of scale 4 (rho 0.63, p value 0.25) or 5 (rho -0.7, p value 0.18) were observed. In conclusion, microelectrode implantation surgeries modified some physiological and pathological behaviours; therefore, it is important to consider this fact when it is working with animal models.

Improving the translational hit of experimental treatments in multiple sclerosis

2010 ◽  
Vol 16 (9) ◽  
pp. 1044-1055 ◽  
Author(s):  
Hanna M Vesterinen ◽  
Emily S Sena ◽  
Charles ffrench-Constant ◽  
Anna Williams ◽  
Siddharthan Chandran ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Best Practice ◽  
Neurological Diseases ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Animal Experiments ◽  
Clinical Findings ◽  
Reported Study ◽  
Experimental Treatments

Background: In other neurological diseases, the failure to translate pre-clinical findings to effective clinical treatments has been partially attributed to bias introduced by shortcomings in the design of animal experiments. Objectives: Here we evaluate published studies of interventions in animal models of multiple sclerosis for methodological design and quality and to identify candidate interventions with the best evidence of efficacy. Methods: A systematic review of the literature describing experiments testing the effectiveness of interventions in animal models of multiple sclerosis was carried out. Data were extracted for reported study quality and design and for neurobehavioural outcome. Weighted mean difference meta-analysis was used to provide summary estimates of the efficacy for drugs where this was reported in five or more publications. Results: The use of a drug in a pre-clinical multiple sclerosis model was reported in 1152 publications, of which 1117 were experimental autoimmune encephalomyelitis (EAE). For 36 interventions analysed in greater detail, neurobehavioural score was improved by 39.6% (95% CI 34.9—44.2%, p < 0.001). However, few studies reported measures to reduce bias, and those reporting randomization or blinding found significantly smaller effect sizes. Conclusions: EAE has proven to be a valuable model in elucidating pathogenesis as well as identifying candidate therapies for multiple sclerosis. However, there is an inconsistent application of measures to limit bias that could be addressed by adopting methodological best practice in study design. Our analysis provides an estimate of sample size required for different levels of power in future studies and suggests a number of interventions for which there are substantial animal data supporting efficacy.

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