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Understanding Epilepsy Using Ex Vivo Hippocampus Brain Models
Epilepsy is a complex neurological disorder characterized by recurrent seizures that has intrigued researchers for centuries. Among the various brain regions, the hippocampus plays a key role in regulating cognitive functions and memory. Researchers have noticed that the hippocampus is often damaged in association with epilepsy patients.
Creative Biolabs describes the critical role of the hippocampus in neurological function, and the advantages and future prospects of utilizing ex vivo hippocampal brain models in epilepsy research. Based on our advanced neuroscience assay platform, STEMOD™ neuroscience ex vivo models can be generated from cells, transgenic mice, aged rats and mice. For different research purposes, the modeling services we can provide include the following.
| Services | What We Do | Advantages |
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| Custom Neural Differentiation Service | As experienced experts in neuroscience modeling, we offer comprehensive customized neural differentiation services to effectively support your neuroscience research. |
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| Custom Brain Spheroid | For different disease processes, Creative Biolabs can generate various types of brain spheroids for neurology and oncology research. Brain spheroids can be generated from stem cells derived from human hair or skin samples. |
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| Custom Brain Organoid Services | Based on our advanced platform, Creative Biolabs now offers customized brain organoid services, including forebrain organoids, cerebellar organoids, whole brain organoids, and retinal organoids. |
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The Critical Role of the Hippocampus in Neurological Function
Located deep in the temporal lobe of the brain, the hippocampus is a hippocampus-shaped structure that is critical for learning, memory consolidation, and spatial navigation. The hippocampus consists of distinct subregions, such as the dentate gyrus, CA1, CA2, and CA3, which are responsible for coordinating the transition from short-term to long-term memory. Its complex circuitry involves a delicate balance of excitatory and inhibitory neurons that are fine-tuned to ensure proper functioning.
Fig. 1 Coronal slice through the transverse axis of the hippocampus.1
Research has shown that disruptions in hippocampal activity are commonly associated with neurological disorders, including epilepsy. Epilepsy is a chronic disorder characterized by recurrent, unpredictable seizures resulting from abnormal neuronal activity in the brain. Epileptic seizures, an explicit manifestation of these neuronal instabilities, illustrate an agitated equilibrium of excitatory and inhibitory processes within the neuronal network. The myriad of epilepsy types, each with distinct symptoms, indicative factors, and treatments, render it a complex subject of study. Indeed, researchers often associate pathologies involving the hippocampal formation, such as scarring (sclerosis), inflammation (encephalitis), and malformations, with severe forms of epilepsy.
Ex Vivo Hippocampus Brain Models for Epilepsy Research
The hippocampal slice culture models are the most popular among the ex vivo models used in epilepsy research. They provide preserved cytoarchitecture of the hippocampus and other related neural circuits involved in epilepsy.
- Organotypic Hippocampal Slice Culture (OHSCs): OHSCs are thin slices of the hippocampus grown in culture that mimic the in vivo environment. This model allows for the manipulation of individual variables in a controlled setting and can be used for long term studies of cellular and molecular mechanisms. OHSCs also retain their cell morphology and are capable of generating spontaneous epileptic activity.
- Acute Hippocampal Slices: This model involves thin slices of hippocampus prepared immediately prior to experimentation. These slices are often used in electrophysiological studies and are useful for studying immediate responses to drugs or other interventions.
- Chronic Epileptic Hippocampal Slice Cultures: These are slice cultures derived from animals that have been induced to become epileptic. They can be maintained for several weeks to months and are useful for studying chronic effects of epilepsy.
- 3D Hippocampal Cultures: These models use a three-dimensional matrix or hippocampus organoid to allow neurons to grow in a more in vivo -like manner. They can more closely mimic the complex neural networks present in the living brain.
- Genetically Modified Ex Vivo Models - These models involve genetically modifying the hippocampal slices, either through the use of transgenic animals or direct genetic manipulation of the slices. These models can be used to study the role of specific genes in epilepsy.
These models provide researchers with a controlled environment to study the cellular and molecular mechanisms behind epileptic seizures. In addition, ex vivo models allow for the manipulation and precise control of experimental variables, thereby improving the reproducibility of results.
Recent Findings Using Ex Vivo Models
The use of ex vivo models has led to several significant discoveries in understanding epilepsy.
| Models | Significant Discoveries |
|---|---|
| Hippocampus | Scientists have observed a prolonged 'hyperexcitable' period following seizure activity in the hippocampus, confirming the theory of a seizure-induced refractory period. |
| Hippocampal slices | Another significant finding is the role of certain genes and ion channels in epilepsy development. Utilizing hippocampal slices, researchers found that dysfunction of the ion channels related to the neurotransmitter GABA is associated with epilepsy |
| Hippocampal slice cultures | Researchers have identified the phenomenon of 'epileptogenesis', involving neuronal death, synaptic reorganization, and the formation of abnormal neural circuits leading to epilepsy development. |
Advantages and Future Prospects
The ex vivo model enables researchers to focus on the contribution of the hippocampus to epilepsy, and the controlled experimental conditions allow researchers to manipulate and control various experimental parameters.
- The ex vivo hippocampal brain model facilitates detailed electrophysiological studies, enabling high-precision measurements of neuronal activity and synaptic transmission. This allows researchers to explore abnormal electrical patterns associated with epilepsy and identify potential targets for intervention.
- Researchers can use ex vivo models to assess the effects of drugs on epileptic activity.
- Ex vivo models provide the opportunity for long-term monitoring, allowing researchers to observe changes in the hippocampus over time.
As epilepsy research using ex vivo hippocampal brain models continues to evolve, technological and methodological advances are expected to enhance the relevance and applicability of ex vivo models in epilepsy research.
- Combining advanced imaging techniques, such as two-photon microscopy and functional magnetic resonance imaging (fMRI)
- Development of 3D culture systems
- High-resolution recordings and the integration of advanced fluorescent sensors
The use of ex vivo hippocampal brain models to understand epilepsy is a dynamic and promising avenue of research, and Creative Biolabs recognizes its importance and is committed to delivering ex vivo brain modeling services with innovative and high-quality scientific solutions.
Reference
- Knierim James J. "The hippocampus." Current Biology 25.23 (2015): R1116-R1121.
For Research Use Only. Not For Clinical Use.