Is the cell death in mesial temporal sclerosis apoptotic?
OBJECTIVE
Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures.


METHODS
We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 +/- 8 years).


RESULTS
Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in approximately 10% of these neurons. Despite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining.


CONCLUSIONS
These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility.
Uysal
Hilmi
H
Department of Neurology, Sevgi Hospital, Hacettepe University Hospitals, Ankara, Turkey.
Cevik
Isin Unal
IU
Soylemezoglu
Figen
F
Elibol
Bulent
B
Ozdemir
Yasemin Gursoy
YG
Evrenkaya
Tulay
T
Saygi
Serap
S
Dalkara
Turgay
T
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000328:Adult; D017668:Age of Onset; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology / Q000473:pathology; D002452:Cell Count; D016923:Cell Death; D053938:DNA Fragmentation; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009474:Neurons / Q000166:cytology / Q000473:pathology; D012598:Sclerosis; D013702:Temporal Lobe / Q000473:pathology*