Hiroki Kitaura1, Tetsuya Hiraishi2, Yosuke Itoh3, Makoto Oishi2, Yukihiko Fujii2, Masafumi Fukuda3, Akiyoshi Kakita4. 1. Department of Pathology, Brain Research Institute, Niigata University, Japan. Electronic address: kitaura@bri.niigata-u.ac.jp. 2. Department of Neurosurgery, Brain Research Institute, Niigata University, Japan. 3. Department of Neurosurgery, NHO Nishiniigata Chuo Hospital, Japan. 4. Department of Pathology, Brain Research Institute, Niigata University, Japan.
Abstract
OBJECTIVE: Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. METHODS: To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. RESULTS: Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. CONCLUSION: These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.
OBJECTIVE: Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. METHODS: To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. RESULTS: Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. CONCLUSION: These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.
Authors: Carlos Castillo-Rangel; Gerardo Marín; Karla Aketzalli Hernandez-Contreras; Cristofer Zarate-Calderon; Micheel Merari Vichi-Ramirez; Wilmar Cortez-Saldias; Marco Antonio Rodriguez-Florido; Ámbar Elizabeth Riley-Moguel; Omar Pichardo; Osvaldo Torres-Pineda; Helena G Vega-Quesada; Ramiro Lopez-Elizalde; Jaime Ordoñez-Granja; Hugo Helec Alvarado-Martinez; Luis Andrés Vega-Quesada; Gonzalo Emiliano Aranda-Abreu Journal: Life (Basel) Date: 2022-08-07