Related Experiment Video
Updated: Jun 24, 2025
Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury
Published on: December 4, 2013
Hippocampus under Pressure: Molecular Mechanisms of Development of Cognitive Impairments in SHR Rats
Mikhail Yu Stepanichev1, Diana I Mamedova2, Natalia V Gulyaeva2
1Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 117485, Russia. m_stepanichev@ihna.ru.
Insights
Chronic hypertension in Spontaneously Hypertensive Rats (SHR) leads to hippocampal changes, contributing to vascular dementia. These SHR rats serve as a valuable model for understanding hypertension-related cognitive impairments.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Pathology
Background:
- Clinical trials and animal studies link chronic hypertension to cognitive decline.
- Spontaneously Hypertensive Rats (SHR) are a genetic model for essential hypertension and vascular dementia.
Purpose of the Study:
- To review structural and biochemical alterations in the hippocampus of SHR rats.
- To explore the role of hypertension and hypothalamic-pituitary-adrenal axis dysfunction in hippocampal changes.
Main Methods:
- Review of existing data on SHR rat models.
- Analysis of structural and molecular changes in the hippocampus.
Main Results:
- Hypertension and neurohumoral dysfunction in SHR rats are associated with vascular pathology and blood-brain barrier impairment.
- Hippocampal alterations include neuroinflammation, impaired neurogenesis, synaptic/neuronal damage, and dysfunction of glucocorticoid receptors, neurotransmitter systems, and BDNF.
- These changes lead to hippocampus dysfunction, impacting cognitive functions.
Conclusions:
- SHR rats exhibit significant structural and biochemical changes in the hippocampus relevant to vascular dementia.
- The SHR rat model demonstrates translational validity for studying mechanisms of vascular dementia.
- Dysfunction of the hypothalamic-pituitary-adrenal system may be a key factor in SHR rat hippocampal pathology.
Abstract:
Data from clinical trials and animal experiments demonstrate relationship between chronic hypertension and development of cognitive impairments. Here, we review structural and biochemical alterations in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension and vascular dementia. In addition to hypertension, dysfunction of the hypothalamic-pituitary-adrenal system observed in SHR rats already at an early age may be a key factor of changes in the hippocampus at the structural and molecular levels. Global changes at the body level, such as hypertension and neurohumoral dysfunction, are associated with the development of vascular pathology and impairment of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus, including dysfunction of steroid hormones receptors, impairments of neurotransmitter systems, BDNF deficiency, oxidative stress, and neuroinflammation are accompanied by the structural alterations, such as cellular signs of neuroinflammation micro- and astrogliosis, impairments of neurogenesis in the subgranular neurogenic zone, and neurodegenerative processes at the level of synapses, axons, and dendrites up to the death of neurons. The consequence of this is dysfunction of hippocampus, a key structure of the limbic system necessary for cognitive functions. Taking into account the available results at various levels starting from the body and brain structure (hippocampus) levels to molecular one, we can confirm translational validity of SHR rats for modeling mechanisms of vascular dementia.
