Perforant path damage results in progressive neuronal death and somal atrophy in layer II of entorhinal cortex and functional impairment with increasing postdamage age
Open accessAbstract
In vivo model systems that can evaluate neuronal death, survival, and regeneration are critical to revealing basic mechanisms of neuronal response and developing strategies for CNS repair. We propose a distinct experimental model of CNS degeneration following lesions to the perforant path connecting the hippocampus and the entorhinal cortex. Within 2 weeks of a unilateral aspirative perforant path lesion, 30% of the ipsilateral entorhinal cortex layer II (ECL II) projection neurons had died with no change in the contralateral ECL II population. Although there was no loss of ECL II neurons with normal aging, animals that survived for 15 months postlesion experienced an almost 50% loss of ipsilateral neurons compared to unlesioned controls. This progressive neuronal death was bilateral, with the contralateral ECL II experiencing a 30% decline in neuronal number relative to unlesioned controls. The use of unbiased stereology ensured that estimates of total number were not distorted by changes in the reference volume. The documented progressive neuronal death resulted in delayed behavioral impairment in spatial learning and performance (latency nearly 200% of controls). We propose, therefore, that the perforant path model is suitable for experimental investigation of neuronal survival and regeneration following CNS trauma.
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Perforant path transections typically induce death in 20% of neurons in layer II of the entorhinal cortex.
“we subjected rats to perforant path transections that typically induce death in 20% of neurons in layer II of the entorhinal cortex20.”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [20]
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- Authors
- Peterson, D., Lucidi-Phillipi, C., Eagle, K., & Gage, F.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1994-11-01
- Volume
- 14
- Issue
- 11
- Pages
- 6872-6885
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6577234
- OpenAlex
- W1525773819
- Cited by
- 45
- References
- 58
- Citations by year
- 2026: 1 · 2020: 1 · 2019: 1 · 2014: 1
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG010435, R01-AG-06088, R01AG006088, P01 AG 10435)
- National Institute of Neurological Disorders and Stroke (P01NS028121, P01 NS-28121)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neuronal cell death, hippocampus, spatial learning impairment, aging, neuronal survival, neuronal regeneration, stereology
- MeSH terms
- Aging, Animals, Disease Models, Animal, Female, Hippocampus, Nerve Degeneration, Nerve Regeneration, Neural Pathways, Neurons, Rats, Inbred F344, Reproducibility of Results, Cell Death, Entorhinal Cortex, Maze Learning, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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