A Novel In Vivo Model for Multiplexed Analysis of Callosal Connections upon Cortical Damage
(2022) In International Journal of Molecular Sciences 23(15).- Abstract
Brain damage is the major cause of permanent disability and it is particularly relevant in the elderly. While most studies focused on the immediate phase of neuronal loss upon injury, much less is known about the process of axonal regeneration after damage. The development of new refined preclinical models to investigate neuronal regeneration and the recovery of brain tissue upon injury is a major unmet challenge. Here, we present a novel experimental paradigm in mice that entails the (i) tracing of cortico-callosal connections, (ii) a mechanical lesion of the motor cortex, (iii) the stereological and histological analysis of the damaged tissue, and (iv) the functional characterization of motor deficits. By combining conventional... (More)
Brain damage is the major cause of permanent disability and it is particularly relevant in the elderly. While most studies focused on the immediate phase of neuronal loss upon injury, much less is known about the process of axonal regeneration after damage. The development of new refined preclinical models to investigate neuronal regeneration and the recovery of brain tissue upon injury is a major unmet challenge. Here, we present a novel experimental paradigm in mice that entails the (i) tracing of cortico-callosal connections, (ii) a mechanical lesion of the motor cortex, (iii) the stereological and histological analysis of the damaged tissue, and (iv) the functional characterization of motor deficits. By combining conventional microscopy with semi-automated 3D reconstruction, this approach allows the analysis of fine subcellular structures, such as axonal terminals, with the tridimensional overview of the connectivity and tissue integrity around the lesioned area. Since this 3D reconstruction is performed in serial sections, multiple labeling can be performed by combining diverse histological markers. We provide an example of how this methodology can be used to study cellular interactions. Namely, we show the correlation between active microglial cells and the perineuronal nets that envelop parvalbumin interneurons. In conclusion, this novel experimental paradigm will contribute to a better understanding of the molecular and cellular interactions underpinning the process of cortical regeneration upon brain damage.
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- author
- González-Manteiga, Ana ; Navarro-González, Carmen ; Sebestyén, Valentina Evita ; Saborit-Torres, Jose Manuel ; Talhada, Daniela LU ; Vayá, María de la Iglesia ; Ruscher, Karsten LU and Fazzari, Pietro
- organization
- publishing date
- 2022-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- brain damage, callosal neurons, cortico-cortical connections, microglia, neuronal regeneration, perineuronal network, pre-clinical models, stroke, traumatic injury
- in
- International Journal of Molecular Sciences
- volume
- 23
- issue
- 15
- article number
- 8224
- publisher
- MDPI AG
- external identifiers
-
- scopus:85137099851
- pmid:35897791
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms23158224
- language
- English
- LU publication?
- yes
- id
- e7e123ce-5ea5-4eb7-9332-a2ca7a18b6a6
- date added to LUP
- 2022-11-09 12:13:55
- date last changed
- 2024-05-30 13:51:49
@article{e7e123ce-5ea5-4eb7-9332-a2ca7a18b6a6,
abstract = {{<p>Brain damage is the major cause of permanent disability and it is particularly relevant in the elderly. While most studies focused on the immediate phase of neuronal loss upon injury, much less is known about the process of axonal regeneration after damage. The development of new refined preclinical models to investigate neuronal regeneration and the recovery of brain tissue upon injury is a major unmet challenge. Here, we present a novel experimental paradigm in mice that entails the (i) tracing of cortico-callosal connections, (ii) a mechanical lesion of the motor cortex, (iii) the stereological and histological analysis of the damaged tissue, and (iv) the functional characterization of motor deficits. By combining conventional microscopy with semi-automated 3D reconstruction, this approach allows the analysis of fine subcellular structures, such as axonal terminals, with the tridimensional overview of the connectivity and tissue integrity around the lesioned area. Since this 3D reconstruction is performed in serial sections, multiple labeling can be performed by combining diverse histological markers. We provide an example of how this methodology can be used to study cellular interactions. Namely, we show the correlation between active microglial cells and the perineuronal nets that envelop parvalbumin interneurons. In conclusion, this novel experimental paradigm will contribute to a better understanding of the molecular and cellular interactions underpinning the process of cortical regeneration upon brain damage.</p>}},
author = {{González-Manteiga, Ana and Navarro-González, Carmen and Sebestyén, Valentina Evita and Saborit-Torres, Jose Manuel and Talhada, Daniela and Vayá, María de la Iglesia and Ruscher, Karsten and Fazzari, Pietro}},
issn = {{1661-6596}},
keywords = {{brain damage; callosal neurons; cortico-cortical connections; microglia; neuronal regeneration; perineuronal network; pre-clinical models; stroke; traumatic injury}},
language = {{eng}},
number = {{15}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{A Novel In Vivo Model for Multiplexed Analysis of Callosal Connections upon Cortical Damage}},
url = {{http://dx.doi.org/10.3390/ijms23158224}},
doi = {{10.3390/ijms23158224}},
volume = {{23}},
year = {{2022}},
}