Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion
Abstract
Inhibitors of cell-swelling-activated anion channels, including the antiestrogenic compound tamoxifen (TAM), have been shown to attenuate the increase in excitatory amino acids (EAA) during ischemia. Since TAM enters the CNS we tested whether it provides protection from damage due to reversible middle cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 25 min before ischemia, potently reduced the total volume of the infarct from 328 +/- 34 mm3 to 41 +/- 21 mm3, a reduction of 87%, as measured by TTC staining. It was equally effective when infused starting at 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was also found histologically. TAM had no effect on CBF as measured by hydrogen clearance. This appears to be the first report of a marked neuroprotective effect of TAM. Further studies are needed to determine whether its effects are due to inhibition of EAA release and/or other potential neuroprotective sites of action.
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Tamoxifen has shown neuroprotective effects in models of stroke, dementia, multiple sclerosis, Parkinson's disease, traumatic brain injury, and spinal cord injury.
“tamoxifen crosses the blood-brain barrier [32] and has shown neuroprotective effects in models of stroke [33], dementia [34], multiple sclerosis [35], Parkinson’s disease [36], traumatic brain injury [37], and SCI [38].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [33]
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Tripathi, R. B., Rivers, L. E., Young, K. M., Jamen, F., & Richardson, W. D. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3411-10.2010 · Cited by 277 · see citing works
Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy
Kimelberg, H. K. (2005) · Glia · doi:10.1002/glia.20174 · Cited by 257 · see citing works
Self-citationColón, J. M., Torrado, A. I., Cajigas, Á., Santiago, J. M., Salgado, I. K., Arroyo, Y., & Miranda, J. D. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4111 · Cited by 35 · see citing works
Pukos, N., & McTigue, D. M. (2020) · PLOS ONE · doi:10.1371/journal.pone.0235232 · Cited by 9 · see citing works
- Authors
- Kimelberg, H. K., Feustel, P. J., Jin, Y., Paquette, J., Boulos, A., Keller, R. W., & Tranmer, B. I.
- Affiliations
- Albany Medical College (US)
- Venue
- NeuroReport
- Published
- 2000-08
- Volume
- 11
- Issue
- 12
- Pages
- 2675-2679
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W1979536838
- Cited by
- 108
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 35)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- tamoxifen, neuroprotection, middle cerebral artery occlusion, cerebral ischemia, excitatory amino acids, cell swelling, anion channels, infarct size, reperfusion, cerebral blood flow, antiestrogens
- MeSH terms
- Animals, Arterial Occlusive Diseases, Blood Pressure, Cell Survival, Cerebral Arteries, Cerebral Infarction, Brain Ischemia, Cerebrovascular Circulation, Male, Neurons, Tamoxifen, Time Factors, Rats, Sprague-Dawley, Neuroprotective Agents, Rats
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