Behavioral Impairments in Rats with Focal Cortical Dysplasia Following Febrile Seizures

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Аннотация

Disruptions in cerebral cortex development during early ontogenesis often lead to pharmacoresistant epilepsy and mental disorders. One such disruption is focal cortical dysplasia (FCD), which can be modeled in experimental animals by inducing cryogenic injury to the neocortex on the first day after birth. FCD is frequently associated with the development of epilepsy and behavioral impairments, such as deficits in learning, memory, and social interaction. These effects may be more pronounced when the brain is exposed to additional challenges, such as the combination of FCD with neonatal febrile seizures (FS). However, the specific characteristics of behavioral impairments in this combined pathology remain poorly understood. This study aimed to investigate behavioral impairments in adult male Wistar rats with FCD who had experienced FS. FCD was induced in rat pups on the first day of life (P0) by localized freezing of the somatosensory cortex. On the 10th day of life (P10), FS were triggered in the rat pups through hyperthermia (exposure to warm air) for 30 minutes. Only animals with FS lasting at least 15 minutes were included in the study. The control group consisted of sham-operated rat pups that were separated from their mother for 30 minutes at P10 without exposure to heat. At 2–2.5 months of age, the animals' behavior was evaluated using the following tests: Open Field, Elevated Plus Maze, Social Interaction Test, and Spontaneous Alternation Test in the Y-Maze. The results revealed that the combination of FCD and FS in early life led to increased social activity and alterations in exploratory behavior and anxiety levels in adult rats. These findings suggest that the combined pathology selectively affects behavioral functions, potentially due to the reorganization of neural networks in the brain. The study expands our understanding of the consequences of FCD and FS on brain function development and highlights the need for further research into the mechanisms underlying these changes. This work may contribute to the development of new therapeutic strategies for patients with similar conditions.

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Авторлар туралы

O. Zubareva

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: zubarevaOE@mail.ru
Ресей, Saint Petersburg

D. Sinyak

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: zubarevaOE@mail.ru
Ресей, Saint Petersburg

M. Subhankulov

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: zubarevaOE@mail.ru
Ресей, Saint Petersburg

T. Postnikova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: zubarevaOE@mail.ru
Ресей, Saint Petersburg

A. Zaytsev

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: zubarevaOE@mail.ru
Ресей, Saint Petersburg

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2. Fig. 1. Freezing-induced cortical malformation. (a) - Representative example of a rat brain (P21) that sustained freezing-induced damage at age P0, resulting in a longitudinal microhyria in the left sensorimotor cortex (dashed line). (b) - Schematic representation of freezing-induced microhyria. (c) - Representative example of Nissl stained coronal slices through a dysplastic lesion in the rat cerebral cortex. The image clearly shows the formed four-layer microgyria. The location of the freezing centre is indicated by the black arrow.

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3. Fig. 2. Motor activity of control (Ctrl) and experimental (FCD + FC) rats. (a) - Tracks in the Open Field test. (b) - Distance travelled in the Open Field test. (c) - Speed of locomotion in the Open Field test. (d) - Locomotion time in the Open Field. (e) - Number of arms examined in the ‘Y-maze’ test.

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4. Fig. 3. Exploratory activity of control (Ctrl) and experimental (FCD + FC) rats. (a, b) - Number and time of examinations of burrows in the ‘Open field’ test. (c, d) - Mean time and number of examinations of the same objects in the ‘Exploration and recognition of new objects’ test. * - p < 0.05; Student's t-test.

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5. Fig. 4. Anxiety level scores of control (Ctrl) and experimental (FCD + FC) rats. (a-c) - Absolute and relative time spent in open and closed arms in the Elevated Cross Maze test. (d, e) - Number of episodes and grooming time in the Open Field test. * - p < 0.05; Student's t-test.

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6. Fig. 5. Social behaviour of control (Ctrl) and experimental (FCD + FC) rats in the ‘Social Test’. (a) - Total communication time. (b) - Sniffing the genital area. (c) - Body sniffing and grooming. (d) - Duration of aggressive behaviour. * - p < 0.05; *** - p < 0.001; Student's t-test.

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7. Fig. 6. Memory performance of control (Ctrl) and experimental (FCD + FC) rats in the ‘Y-maze’ test (a, b) and in the ‘Recognition of new objects’ test (c, d). Data are presented as mean and standard error of the mean (a, c, d) or as medians and interquartile ranges (b). & - Differences in the time course of familiar and novel objects in the control group; # - differences in the time course of familiar and novel objects in the experimental group; p < 0.05; paired t-test with Bonferroni correction.

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