What is seizure?
A seizure is a sudden, uncontrolled electrical disturbance in the brain that can cause changes in behavior, movements, feelings, or levels of consciousness. Seizures can vary widely in their presentation and severity, ranging from brief episodes of staring or confusion to convulsions and loss of consciousness.
During a seizure, the normal electrical activity of the brain is disrupted, leading to abnormal synchronized firing of neurons. This abnormal electrical activity can spread rapidly throughout the brain, causing various symptoms depending on the area of the brain affected.
Seizures are classified into two main types:
- Generalized Seizures: Generalized seizures involve abnormal electrical activity throughout the entire brain from the onset of the seizure. They can cause loss of consciousness and may involve convulsive movements such as tonic-clonic (formerly known as grand mal) seizures, in which the person experiences stiffening (tonic phase) followed by jerking movements (clonic phase). Other types of generalized seizures include absence seizures (formerly known as petit mal), myoclonic seizures, and atonic seizures.
- Partial (Focal) Seizures: Partial seizures originate in a specific area of the brain and may or may not spread to involve the entire brain. These seizures can be further classified into simple partial seizures, which do not cause loss of consciousness, and complex partial seizures, which may result in altered consciousness or impaired awareness. Depending on the area of the brain affected, partial seizures can cause various symptoms such as abnormal movements, sensory disturbances, emotional changes, or cognitive impairment.
What is the relationship between seizure and oxidative stress?
The relationship between seizures and oxidative stress is complex and multifaceted. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them or repair the resulting damage. Several lines of evidence suggest that oxidative stress may contribute to the pathophysiology of seizures and epilepsy:
- Increased ROS Production During Seizures: Seizures are associated with increased metabolic activity and excitatory neurotransmitter release in the brain, which can lead to the generation of ROS and reactive nitrogen species (RNS). These reactive species can damage cellular components such as lipids, proteins, and DNA, contributing to neuronal injury and cell death.
- Mitochondrial Dysfunction: Mitochondria are the primary producers of ROS within cells and are also vulnerable to oxidative damage. Studies have shown that mitochondrial dysfunction, including impaired electron transport chain activity and decreased antioxidant defenses, may play a role in seizure-induced oxidative stress.
- Glutathione Depletion: Glutathione is a key antioxidant molecule that helps neutralize ROS and maintain cellular redox balance. Decreased levels of glutathione and other antioxidant enzymes have been observed in animal models of seizures and epilepsy, suggesting an impairment of antioxidant defenses in the epileptic brain.
- Inflammatory Response: Seizures can trigger an inflammatory response in the brain, characterized by the activation of microglia and astrocytes, and the release of pro-inflammatory cytokines and chemokines. This neuroinflammatory response can further exacerbate oxidative stress and contribute to neuronal damage and epileptogenesis.
- Role of Excitotoxicity: Excitotoxicity, or excessive activation of excitatory neurotransmitter receptors such as glutamate receptors, is a hallmark of seizures and epilepsy. Excitotoxicity can lead to calcium influx, mitochondrial dysfunction, and ROS generation, ultimately contributing to neuronal hyperexcitability and seizure activity.
- Antioxidant Therapies: Preclinical studies have shown that antioxidant treatments, such as administration of exogenous antioxidants or enhancement of endogenous antioxidant defenses, can reduce seizure severity and improve seizure outcomes in animal models of epilepsy. These findings suggest that targeting oxidative stress pathways may have therapeutic potential in the management of seizures and epilepsy.
Overall, while the precise mechanisms underlying the relationship between seizures and oxidative stress are still being elucidated, accumulating evidence supports the notion that oxidative stress contributes to the pathophysiology of seizures and epilepsy.