Dataset Information

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain.

ABSTRACT:

Introduction

We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy.

Methods

Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurements, and body temperature (Tb) measurements were taken via temperature sensors implanted in the abdominal cavities of the animals.

Results

No significant difference was observed between the WAR and Wistar control group with respect to the thermoregulatory response elicited by exposure to both acute hypercapnia and acute hypoxia (p>0.05). However, we found that the VE of WARs was attenuated relative to that of Wistar control animals during exposure to both hypercapnic (WAR: 133 ± 11% vs. Wistar: 243 ± 23%, p<0.01) and hypoxic conditions (WAR: 138 ± 8% vs. Wistar: 177 ± 8%; p<0.01). In addition, we noted that this ventilatory attenuation was followed by alterations in the behavioral responses of these animals.

Conclusions

Our results indicate that WARs, a genetic model of epilepsy, have important alterations in their ability to compensate for changes in levels of various arterial blood gasses. WARs present an attenuated ventilatory response to an increased PaCO2 or decreased PaO2, coupled to behavioral changes, which make them a suitable model to further study respiratory risks associated to epilepsy.

SUBMITTER: Granjeiro EM

PROVIDER: S-EPMC4858153 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain.

Granjeiro Érica Maria ÉM da Silva Glauber S F GS Giusti Humberto H Oliveira José Antonio JA Glass Mogens Lesner ML Garcia-Cairasco Norberto N

PloS one 20160505 5

<h4>Introduction</h4>We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy.<h4>Methods</h4>Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurem ...[more]

PMID: 27149672

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Project description:Audiogenic epilepsy (AE), developing in rodent strains in response to loud sound, is widely used as the model of generalized convulsive epilepsy. The molecular and genetic mechanisms that determine the expression of AE are currently non well understood. In the present work we compared transcriptomes from the inferior and superior colliculi (corpora quadrigemina), the crucial epileptogenic midbrain zone for AE in order to identify genes associated to the AE phenotype. Transcriptomes of rats from three strains were compared: Krushinsky-Molodkina (KM) strain (100% AE-prone); Wistar outbred rats (with no AE proneness) and "0" strain, selected from F2 KMxWistar hybrids for the lack of AE. It is shown that KM strain gene expression profile have a number of characteristic differences from those of Wistar and "0" strains. In particular, KM has increased expression of a number of genes involved in positive regulation of the MAPK signaling cascade, as well as genes, responsible for positive regulation of apoptotic processes. The next characteristic difference between the KM strain from Wistar and "0" is a multiple increase in the expression level of the Ttr gene, which is known to be associated with family amyloid polyneuropathy in humans. Further, the KM strain showed a significant decrease in the expression of the Msh3 gene involved in the DNA mismatch repair system, Acsm5, coding a mitochondrial acyl-CoA synthetase specific for medium chain family member 5, and in a number of genes of the oxidative phosphorylation system, and a number of some other genes. Our data confirm the complex multigenic nature of AE inheritance in rodents. A comparison with the data obtained from other AE rodent strains suggests that the convulsive phenotype could develop differently in audiogenic rat strains selected independently. Although, the finding of parallel differences in certain genes expression in AE-prone hamsters (another rodent species) indicate the common (and crucial) neurogenetic defects, leading to AE phenotype in rodents in general.

Project description:Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood-brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

Dataset Information

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain.

Introduction

Methods

Results

Conclusions

Publications

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain.

Similar Datasets

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