Excitatory amino acid transporter 2 downregulation correlates with thalamic neuronal death following kainic acid-induced status epilepticus in rat.

Abstract

Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS.

• Authors: Masashi Sakurai, Haruna Kurokawa, Akinori Shimada, Kazuhiro Nakamura, Hajime Miyata, Takehito Morita
• Journal: Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) Vol. 35 Issue 1 Pg. 1-9 (Feb 2015) ISSN: 1440-1789 [Electronic] Australia
• PMID: 25059512 (Publication Type: Journal Article)
• Copyright: © 2014 Japanese Society of Neuropathology.

Chemical References

• Excitatory Amino Acid Transporter 2
• Slc1a2 protein, rat
• Kainic Acid

Topics

• Animals
• Astrocytes (metabolism)
• Cell Death
• Down-Regulation
• Excitatory Amino Acid Transporter 2 (metabolism)
• Kainic Acid
• Magnetic Resonance Spectroscopy
• Male
• Microglia (metabolism)
• Midline Thalamic Nuclei (blood supply, metabolism, pathology)
• Neurons (cytology, physiology)
• Rats
• Rats, Sprague-Dawley
• Status Epilepticus (chemically induced, metabolism, pathology)