Limits...
Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

Tzekov R, Dawson C, Orlando M, Mouzon B, Reed J, Evans J, Crynen G, Mullan M, Crawford F - PLoS ONE (2016)

Bottom Line: These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs.Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D.The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased.

View Article: PubMed Central - PubMed

Affiliation: The Roskamp Institute, Sarasota, FL, United States of America.

ABSTRACT
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.

No MeSH data available.


Related in: MedlinePlus

Leucocyte infiltration and microglial activation in optic nerve after r-mTBI.Staining for leucocyte marker CD45 of sections of optic nerves 3 weeks after repetitive anesthesia alone (r-sham) (A) and r-mTBI (B). Ionized calcium-binding adaptor molecule 1 (Iba-1) immunostain of longitudinal sections of optic nerves at the same time point 3 weeks after repetitive anesthesia alone (r-sham) (C) and r-mTBI (D). Higher magnification insets provide further detail, in particular a CD45+ cluster of cells (inset in panel B) and triangularly shaped iba-1+ cells (inset in panel D, arrows).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835061&req=5

pone.0153608.g003: Leucocyte infiltration and microglial activation in optic nerve after r-mTBI.Staining for leucocyte marker CD45 of sections of optic nerves 3 weeks after repetitive anesthesia alone (r-sham) (A) and r-mTBI (B). Ionized calcium-binding adaptor molecule 1 (Iba-1) immunostain of longitudinal sections of optic nerves at the same time point 3 weeks after repetitive anesthesia alone (r-sham) (C) and r-mTBI (D). Higher magnification insets provide further detail, in particular a CD45+ cluster of cells (inset in panel B) and triangularly shaped iba-1+ cells (inset in panel D, arrows).

Mentions: To investigate the cellular origin of the increased cellularity after r-mTBI, optic nerves were stained for CD45 and Iba-1, markers for leucocytes and microglia, respectively. A slight increase in leukocyte presence was noted, while there was a marked increase in the expression of Iba-1, suggestive of microglial cells as the main driver for increased cellularity (Fig 3). The areas of increased presence of leucocytes and microglia were overlapping with the areas of more pronounced myelin loss in the central part of the optic nerve. Staining with S100B antibodies, which would have indicated astrocytosis and axonal proliferation, did not reveal any increase in staining in r-mTBI optic nerves (data not shown).


Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

Tzekov R, Dawson C, Orlando M, Mouzon B, Reed J, Evans J, Crynen G, Mullan M, Crawford F - PLoS ONE (2016)

Leucocyte infiltration and microglial activation in optic nerve after r-mTBI.Staining for leucocyte marker CD45 of sections of optic nerves 3 weeks after repetitive anesthesia alone (r-sham) (A) and r-mTBI (B). Ionized calcium-binding adaptor molecule 1 (Iba-1) immunostain of longitudinal sections of optic nerves at the same time point 3 weeks after repetitive anesthesia alone (r-sham) (C) and r-mTBI (D). Higher magnification insets provide further detail, in particular a CD45+ cluster of cells (inset in panel B) and triangularly shaped iba-1+ cells (inset in panel D, arrows).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835061&req=5

pone.0153608.g003: Leucocyte infiltration and microglial activation in optic nerve after r-mTBI.Staining for leucocyte marker CD45 of sections of optic nerves 3 weeks after repetitive anesthesia alone (r-sham) (A) and r-mTBI (B). Ionized calcium-binding adaptor molecule 1 (Iba-1) immunostain of longitudinal sections of optic nerves at the same time point 3 weeks after repetitive anesthesia alone (r-sham) (C) and r-mTBI (D). Higher magnification insets provide further detail, in particular a CD45+ cluster of cells (inset in panel B) and triangularly shaped iba-1+ cells (inset in panel D, arrows).
Mentions: To investigate the cellular origin of the increased cellularity after r-mTBI, optic nerves were stained for CD45 and Iba-1, markers for leucocytes and microglia, respectively. A slight increase in leukocyte presence was noted, while there was a marked increase in the expression of Iba-1, suggestive of microglial cells as the main driver for increased cellularity (Fig 3). The areas of increased presence of leucocytes and microglia were overlapping with the areas of more pronounced myelin loss in the central part of the optic nerve. Staining with S100B antibodies, which would have indicated astrocytosis and axonal proliferation, did not reveal any increase in staining in r-mTBI optic nerves (data not shown).

Bottom Line: These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs.Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D.The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased.

View Article: PubMed Central - PubMed

Affiliation: The Roskamp Institute, Sarasota, FL, United States of America.

ABSTRACT
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.

No MeSH data available.


Related in: MedlinePlus