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Int. J. Mol. Sci. 2018, 19(11), 3544; https://doi.org/10.3390/ijms19113544

Immunohistochemical Evaluation of Aquaporin-4 and its Correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 Expressions in Fatal Traumatic Brain Injury

1
Department of Morphology, Experimental Medicine and Surgery, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy
2
Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
3
IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy
4
Institute of Legal Medicine, Department of Surgical Pathology, Medical, Molecular and Critical Area, University of Pisa, Ospedale Santa Chiara, Via Roma 55, 56126 Pisa, Italy
5
Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D’Avanzo, Via degli Aviatori 1, 71100 Foggia, Italy
6
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy
7
Unit of Legal Medicine, ASUR Area Vasta 5, Viale Marcello Federici, 63100 Ascoli Piceno, Italy
*
Author to whom correspondence should be addressed.
Received: 22 August 2018 / Revised: 4 November 2018 / Accepted: 7 November 2018 / Published: 10 November 2018
(This article belongs to the Special Issue Neuroprotective Strategies 2018)
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Abstract

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance. View Full-Text
Keywords: traumatic brain injury; aquaporin; genetic analysis; edema; computed tomography (CT) scan; hypoxia; microglia activation traumatic brain injury; aquaporin; genetic analysis; edema; computed tomography (CT) scan; hypoxia; microglia activation
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Neri, M.; Frati, A.; Turillazzi, E.; Cantatore, S.; Cipolloni, L.; Di Paolo, M.; Frati, P.; La Russa, R.; Maiese, A.; Scopetti, M.; Santurro, A.; Sessa, F.; Zamparese, R.; Fineschi, V. Immunohistochemical Evaluation of Aquaporin-4 and its Correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 Expressions in Fatal Traumatic Brain Injury. Int. J. Mol. Sci. 2018, 19, 3544.

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