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Advanced Neurology Epilepsy after traumatic brain injuries

Figure 1. Graphical illustration of direct brain injury associated with external force. The figure was created using BioRender (https://www.biorender.com/).
Abbreviation: TBI: Traumatic brain injury.

research has made significant strides in unraveling the 2.3. Excitotoxicity and glutamate dysregulation
complex pathogenesis of epilepsy following TBI, revealing Excessive release of excitatory neurotransmitters,
a multifaceted interplay of molecular, cellular, and systemic particularly glutamate, is a hallmark of TBI-induced
mechanisms. There are multiple initial targeted areas after epileptogenesis. Glutamate-mediated excitotoxicity leads
primary and subsequent injury to the brain (Figure 2). to overactivation of NMDA and AMPA receptors, causing
Understanding these research advances and targeted areas
is crucial for developing targeted therapeutic interventions calcium influx, neuronal damage, and increased seizure
and improving outcomes for affected individuals. 19 susceptibility. Novel therapeutic approaches include
the development of glutamate receptor antagonists and
2.1. Neuroinflammation and immune response modulators to reduce excitotoxic effects. 22
Neuroinflammation is a central feature in the pathogenesis 2.4. Aberrant neurogenesis and synaptic
of PTE. Following TBI, the activation of microglia and remodeling
astrocytes leads to the release of pro-inflammatory cytokines
such as interleukin 1β (IL-1β) and tumor necrosis factor- TBI triggers abnormal neurogenesis and synaptic plasticity,
alpha (TNF-α). These inflammatory mediators disrupt contributing to the formation of hyperexcitable neural
the blood-brain barrier (BBB), contribute to neuronal circuits. Aberrant sprouting of mossy fibers and changes
hyperexcitability, and increase the risk of seizure generation. in inhibitory interneuron networks are key processes
Advances in understanding the role of inflammation have in epileptogenesis. Advances in stem cell research and
highlighted potential therapeutic targets, including anti- neuroregenerative therapies offer promising avenues to
inflammatory agents and immune modulators. 20 restore normal neurogenesis and synaptic connectivity. 23

2.2. BBB disruption 2.5. Oxidative stress and mitochondrial dysfunction
TBI-induced BBB disruption facilitates the entry of Oxidative stress and mitochondrial dysfunction play
peripheral immune cells, toxins, and serum proteins into critical roles in the progression of epilepsy after TBI.
the brain parenchyma. This triggers secondary cascades, The excessive production of reactive oxygen species
including oxidative stress and excitotoxicity, which are and impaired mitochondrial function contribute to
implicated in epileptogenesis. Research has focused neuronal death and seizure susceptibility. Antioxidant
on strategies to restore BBB integrity, such as targeting therapies, including the use of mitochondrial protectants,
matrix metalloproteinases and endothelial dysfunction, to are being explored as potential treatments to prevent
mitigate epileptic outcomes. 21 epileptogenesis. 24

Volume 4 Issue 4 (2025) 3 doi: 10.36922/an.8356