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Anteromesial Temporal Lobectomy for Medically Intractable Temporal Lobe Epilepsy: An Operative Study
Published on: August 15, 2025
Mesial temporal lobe epilepsy with psychiatric comorbidities: a place for differential neuroinflammatory interplay
Ludmyla Kandratavicius1,2, Jose Eduardo Peixoto-Santos3, Mariana Raquel Monteiro4
1Department of Neurosciences and Behavior, Ribeirao Preto Medical School, University of Sao Paulo (USP), Av Bandeirantes 3900, CEP 14049-900, Ribeirao Preto, SP, Brazil. ludykandra@gmail.com.
Background:
Despite the strong association between epilepsy and psychiatric comorbidities, few biological substrates are currently described. We have previously reported neuropathological alterations in mesial temporal lobe epilepsy (MTLE) patients with major depression and psychosis that suggest a morphological and neurochemical basis for psychopathological symptoms. Neuroinflammatory-related structures and molecules might be part of the altered neurochemical milieu underlying the association between epilepsy and psychiatric comorbidities, and such features have not been previously investigated in humans.
Methods:
MTLE hippocampi of subjects without psychiatric history (MTLEW), MTLE + major depression (MTLE + D), and MTLE + interictal psychosis (MTLE + P) derived from epilepsy surgery and control necropsies were investigated for reactive astrocytes (glial fibrillary acidic protein (GFAP)), activated microglia (human leukocyte antigen, MHC class II (HLA-DR)), glial metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) immunohistochemistry.
Results:
We found an increased GFAP immunoreactive area in the molecular layers, granule cell layer, and cornus ammonis region 2 (CA2) and cornus ammonis region 1 (CA1) of MTLEW and MTLE + P, respectively, compared to MTLE + D. HLA-DR immunoreactive area was higher in cornus ammonis region 3 (CA3) of MTLE + P, compared to MTLE + D and MTLEW, and in the hilus, when compared to MTLEW. MTLEW cases showed increased MT-I/II area in the granule cell layer and CA1, compared to MTLE + P, and in the parasubiculum, when compared to MTLE + D and MTLE + P. Differences between MTLE and control, such as astrogliosis, microgliosis, increased MT-I/II, and decreased perivascular AQP4 in the epileptogenic hippocampus, were in agreement to what is currently described in the literature.
Conclusions:
Neuroinflammatory-related molecules in MTLE hippocampus show a distinct pattern of expression when patients present with a comorbid psychiatric diagnosis, similar to what is found in the pure forms of schizophrenia and major depression. Future studies focusing on inflammatory characteristics of MTLE with psychiatric comorbidities might help in the design of better therapeutic strategies.
Insights
Neuroinflammation in mesial temporal lobe epilepsy (MTLE) with psychiatric comorbidities shows distinct patterns. These findings in MTLE hippocampi may inform future therapeutic strategies for epilepsy and co-occurring mental health conditions.
Area of Science:
- Neuroscience
- Neuropathology
- Psychiatry
Background:
- Epilepsy and psychiatric comorbidities are strongly linked, but biological underpinnings remain unclear.
- Previous work identified neuropathological alterations in mesial temporal lobe epilepsy (MTLE) with depression and psychosis.
- Neuroinflammation is a potential, yet uninvestigated, factor in the epilepsy-psychiatric comorbidity link.
Purpose of the Study:
- To investigate neuroinflammatory markers in the hippocampi of MTLE patients with and without psychiatric comorbidities.
- To explore the expression patterns of glial fibrillary acidic protein (GFAP), human leukocyte antigen (HLA-DR), metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) in relation to psychiatric status.
Main Methods:
- Hippocampal tissues from epilepsy surgery patients (MTLE without psychiatric history, MTLE with major depression, MTLE with interictal psychosis) and control necropsies were analyzed.
- Immunohistochemistry was used to assess the expression of reactive astrocytes (GFAP), activated microglia (HLA-DR), MT-I/II, and AQP4.
Main Results:
- Increased GFAP immunoreactivity was observed in specific hippocampal regions of MTLE patients without psychiatric history and with psychosis compared to those with depression.
- Higher HLA-DR immunoreactivity was found in the CA3 region and hilus of MTLE patients with psychosis compared to other groups.
- MTLE patients without psychiatric history showed increased MT-I/II in certain regions compared to those with psychosis.
Conclusions:
- Neuroinflammatory markers in the MTLE hippocampus exhibit distinct expression patterns correlating with the presence of psychiatric comorbidities.
- These findings suggest a potential role for neuroinflammation in the pathophysiology of comorbid psychiatric conditions in epilepsy.
- Further research into the inflammatory characteristics of MTLE with psychiatric comorbidities could lead to improved therapeutic interventions.
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