Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion
Chronic cerebral hypoperfusion (CCH) has been indicated to impair cognitive and diverse brain functions. However, the neural mechanisms linking these cerebrovascular and phenotypic alterations remain unclear. Here, we investigated the effect of CCH on neuronal activity in male mice with unilateral common carotid artery occlusion using optical imaging and MRI. Our examinations revealed enhanced neuronal activity in concurrence with increased glutamate and tissue acidosis up to seven days after occlusion. At 21-28 days after occlusion, neuronal activity decreased below baseline, while the acidotic but not the hyperglutamatergic state persisted. Notably, pharmacological blockade of the N-methyl-D-aspartate-type glutamate receptor, initiated at an early stage of CCH, suppressed the onset of neuronal hyperexcitation and subsequent deficits in neuronal activity. Altogether, we provide experimental evidence that CCH induces a glutamate surge and results in neuronal hyperexcitation at an early phase, which thereafter gives rise to a non-lethal but progressive deterioration of neuronal functions.
Authors
- Manami Takahashi (ORCID: https://orcid.org/0000-0003-0829-8780)
- Tetsuro Yamashita (ORCID: https://orcid.org/0000-0002-1047-1290)
- Takuya Urushihata (ORCID: https://orcid.org/0000-0001-7192-2940)
- Naruhiko Sahara (ORCID: https://orcid.org/0000-0003-2122-5797)
- Makoto Higuchi (ORCID: https://orcid.org/0000-0002-9190-7235)
- Kazuto Masamoto (ORCID: https://orcid.org/0000-0002-2958-9627)
- Yuhei Takado (ORCID: https://orcid.org/0000-0001-7484-8424)
- Nobuhiro Nitta
- Takayuki Obata (ORCID: https://orcid.org/0000-0001-7678-5033)
- Iwao Kanno (ORCID: https://orcid.org/0000-0002-1844-406X)
- Hiroshi Ito (ORCID: https://orcid.org/0000-0002-3581-4798)
- Hiroyuki Takuwa (ORCID: https://orcid.org/0000-0003-1166-9845)
- Tetsuya Suhara (ORCID: https://orcid.org/0000-0003-2916-225X)
- Masaya Takahashi (ORCID: https://orcid.org/0000-0002-5938-6249)
- Yosuke Tajima (ORCID: https://orcid.org/0000-0001-6224-819X)
- Masafumi Shimojo (ORCID: https://orcid.org/0000-0001-6231-154X)
- Yutaka Tomita
Institutions
- Fukushima Medical University (JP)
- Iwate University (JP)
- Tohoku University (JP)
- Keio University (JP)
- University of Electro-Communications (JP)
- Juntendo University (JP)
- National Institutes for Quantum Science and Technology (JP)
Publication Details
- Journal
- Journal of Cerebral Blood Flow & Metabolism
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1177/0271678x251328971
- Primary Topic
- Neurological Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00