Effects of long term nitrite therapy on functional recovery in experimental ischemia model
Abstract
Our data have shown that nitrite therapy can rescue the ischemic brain when injected <3h after cerebral ischemic-reperfusion (I/R) injury and its effects can be prolonged to 4.5h in combination with memantine. We investigated whether or not long-term nitrite therapy is beneficial in ischemic brains. Sodium nitrite (1-100 μg/kg ip) or saline were administered to rats subjected to focal I/R injury for 7 days beginning 24h after I/R. Behavioral tests for 5 weeks revealed better functional recovery in the high-dose nitrite group than the control group. Other nitrite groups with relatively low doses showed no functional benefits. Hemispheric atrophy was attenuated by approximately 30% in the high-dose nitrite group. High-dose nitrite therapy also reduced inflammatory cytokine levels and caspase activity in the subacute period, and increased BrdU(+)MAP2(+) and BrdU(+)laminin(+) cells, and vascular density in the 5-week ischemic brain. Long-term nitrite therapy, when initiated 24h after I/R, corrected the subacute hostile environment, induced tissue and vascular regeneration, and improved functional recovery. Early and subsequent long term nitrite therapy may be effective in the management for ischemic stroke patients.
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Low concentrations of nitrite mediate cytoprotection in a variety of tissues in animal models including heart, liver, brain, kidney, hindlimb, and human forearm.
“The efficacy of low concentrations of nitrite in mediating cytoprotection has been demonstrated in a variety of tissues in animal models including heart [8, 9, 55, 118–122] liver [9, 120, 123], brain [124–126], kidney [127, 128], hindlimb [129], and human forearm [23].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [124]
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- Authors
- Jung, K.-H., Chu, K., Lee, S.-T., Sunwoo, J.-S., Park, D.-K., Kim, J.-H., Kim, S., Lee, S. K., Kim, M., & Roh, J.-K.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Roh, Jae-Kyu
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 403
- Issue
- 1
- Pages
- 66-72
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2051751881
- Cited by
- 23
- References
- 25
- Citations by year
- 2024: 1 · 2018: 3 · 2017: 1 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- nitrite therapy, sodium nitrite, cerebral ischemia-reperfusion injury, ischemic stroke, functional recovery, long-term treatment, memantine, hemispheric atrophy, neuroinflammation, caspase activity, neurogenesis, angiogenesis, vessel density, subacute phase
- MeSH terms
- Animals, Brain Ischemia, Disease Models, Animal, Female, Humans, Nitrites, Reperfusion Injury, Cytokines, Rats, Sprague-Dawley, Neovascularization, Physiologic, Recovery of Function, Caspases, Rats, Neurogenesis
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