Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Plasma Concentrations of AQPs in Acute SDH
2.3. Plasma Concentrations of AQPs in Chronic SDH
3. Discussion
4. Materials and Methods
4.1. Study Population and Eligibility Criteria
4.2. Blood Sample Collection, Processing, and Storage
4.3. AQP Concentration Measurements
4.4. Radiological Examination
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Guan, B.; Anderson, D.B.; Chen, L.; Feng, S.; Zhou, H. Original research: Global, regional and national burden of traumatic brain injury and spinal cord injury, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. BMJ Open 2023, 13, e075049. [Google Scholar] [CrossRef] [PubMed]
- Dasic, D.; Morgan, L.; Panezai, A.; Syrmos, N.; Ligarotti, G.K.; Zaed, I.; Chibbaro, S.; Khan, T.; Prisco, L.; Ganau, M. A scoping review on the challenges, improvement programs, and relevant output metrics for neurotrauma services in major trauma centers. Surg. Neurol. Int. 2022, 13, 171. [Google Scholar] [CrossRef] [PubMed]
- Freire, M.A.M.; Rocha, G.S.; Bittencourt, L.O.; Falcao, D.; Lima, R.R.; Cavalcanti, J.R.L.P. Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far? Biology 2023, 12, 1139. [Google Scholar] [CrossRef] [PubMed]
- Al-Adli, N.; Akbik, O.S.; Rail, B.; Montgomery, E.; Caldwell, C.; Barrie, U.; Vira, S.; Al Tamimi, M.; Bagley, C.A.; Aoun, S.G. The Clinical Use of Serum Biomarkers in Traumatic Brain Injury: A Systematic Review Stratified by Injury Severity. World Neurosurg. 2021, 155, e418–e438. [Google Scholar] [CrossRef] [PubMed]
- Szymoniuk, M.; Litak, J.; Sakwa, L.; Dryla, A.; Zezuliński, W.; Czyżewski, W.; Kamieniak, P.; Blicharski, T. Molecular Mechanisms and Clinical Application of Multipotent Stem Cells for Spinal Cord Injury. Cells 2023, 12, 120. [Google Scholar] [CrossRef] [PubMed]
- Schweitzer, A.D.; Niogi, S.N.; Whitlow, C.J.; Tsiouris, A.J. Traumatic brain injury: Imaging patterns and complications. Radiographics 2019, 39, 1571–1595. [Google Scholar] [CrossRef] [PubMed]
- Saito, T.; Arizono, T.; Maeda, T.; Terada, K.; Iwamoto, Y. A novel technique for surgical resection of spinal meningioma. Spine 2001, 26, 1805–1808. [Google Scholar] [CrossRef] [PubMed]
- Hirt, L.; Price, M.; Benakis, C.; Badaut, J. Aquaporins in neurological disorders. Clin. Transl. Neurosci. 2018, 2, 2514183X1775290. [Google Scholar] [CrossRef]
- Rauen, K.; Pop, V.; Trabold, R.; Badaut, J.; Plesnila, N. Vasopressin V1a Receptors Regulate Cerebral Aquaporin 1 after Traumatic Brain Injury. J. Neurotrauma 2020, 37, 665. [Google Scholar] [CrossRef]
- Jung, H.J.; Kwon, T.-H. Molecular mechanisms regulating aquaporin-2 in kidney collecting duct. Am. J. Physiol. Physiol. 2016, 311, F1318. [Google Scholar] [CrossRef]
- Miyazawa, Y.; Mikami, S.; Yamamoto, K.; Sakai, M.; Saito, T.; Yamamoto, T.; Ishibashi, K.; Sasaki, S. AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities. Clin. Exp. Nephrol. 2018, 22, 782–788. [Google Scholar] [CrossRef] [PubMed]
- Czyżewski, W.; Mazurek, M.; Sakwa, L.; Szymoniuk, M.; Pham, J.; Pasierb, B.; Litak, J.; Czyżewska, E.; Turek, M.; Piotrowski, B.; et al. Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury. Cells 2024, 13, 148. [Google Scholar] [CrossRef]
- Zahl, S.; Skauli, N.; Stahl, K.; Prydz, A.; Frey, M.M.; Dissen, E.; Ottersen, O.P.; Amiry-Moghaddam, M. Aquaporin-9 in the Brain Inflammatory Response: Evidence from Mice Injected with the Parkinsonogenic Toxin MPP+. Biomolecules 2023, 13, 588. [Google Scholar] [CrossRef]
- Borsani, E. Aquaporins in Sensory and Pain Transmission. Curr. Neuropharmacol. 2010, 8, 122–127. [Google Scholar] [CrossRef]
- Bielewicz, J.; Kamieniak, M.; Szymoniuk, M.; Litak, J.; Czyżewski, W.; Kamieniak, P. Diagnosis and Management of Neuropathic Pain in Spine Diseases. J. Clin. Med. 2023, 12, 1380. [Google Scholar] [CrossRef] [PubMed]
- Li, B.; Yuan, H.; Li, H.; Luo, B.; Yu, X.; Wang, Y.; Liu, W. Mechanism of Aquaporin-4 Up-Regulation After Traumatic Brain Injury and Preventative Action of Astragalus Polysaccharides in Mice. J. Biomater. Tissue Eng. 2021, 11, 1037–1045. [Google Scholar] [CrossRef]
- Huang, Y.; Li, S.N.; Zhou, X.Y.; Zhang, L.X.; Chen, G.X.; Wang, T.H.; Xia, Q.J.; Liang, N.; Zhang, X. The dual role of aqp4 in cytotoxic and vasogenic edema following spinal cord contusion and its possible as-sociation with energy metabolism via cox5a. Front. Neurosci. 2019, 13, 412964. [Google Scholar] [CrossRef]
- Abdelhak, A.; Foschi, M.; Abu-Rumeileh, S.; Yue, J.K.; D’anna, L.; Huss, A.; Oeckl, P.; Ludolph, A.C.; Kuhle, J.; Petzold, A.; et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat. Rev. Neurol. 2022, 18, 158–172. [Google Scholar] [CrossRef] [PubMed]
- Heiskanen, M.; Jääskeläinen, O.; Manninen, E.; Das Gupta, S.; Andrade, P.; Ciszek, R.; Gröhn, O.; Herukka, S.-K.; Puhakka, N.; Pitkänen, A. Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI. Int. J. Mol. Sci. 2022, 23, 15208. [Google Scholar] [CrossRef]
- Oris, C.; Kahouadji, S.; Durif, J.; Bouvier, D.; Sapin, V. S100B, Actor and Biomarker of Mild Traumatic Brain Injury. Int. J. Mol. Sci. 2023, 24, 6602. [Google Scholar] [CrossRef]
- Badaut, J.; Brunet, J.; Petit, J.-M.; Guérin, C.; Magistretti, P.; Regli, L. Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats. Brain Res. 2008, 1188, 17–24. [Google Scholar] [CrossRef] [PubMed]
- The Relationship between the Aquaporin-4 and Brain Edema, Pathologic Change, Ultrastructure in Peri-Hematoma Tissue in Patients with Intracerebral Hemorrhage—PubMed. Available online: https://pubmed.ncbi.nlm.nih.gov/19000426/ (accessed on 29 April 2024).
- Shi, Y.; Fan, X.; Li, G.; Zhong, D.; Zhang, X. Association of Serum Dystroglycan, MMP-2/9 and AQP-4 with Haematoma Expansion in Patients with Intracerebral Haemorrhage. Neuropsychiatr. Dis. Treat. 2021, 17, 11–18. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Yang, M.; Qiu, G.-P.; Zhuo, F.; Yu, W.-H.; Sun, S.-Q.; Xiu, Y. Aquaporin 9 in rat brain after severe traumatic brain injury. Arq. Neuro-Psiquiatria 2012, 70, 214–220. [Google Scholar] [CrossRef] [PubMed]
- Qiu, B.; Li, X.; Sun, X.; Wang, Y.; Jing, Z.; Zhang, X.; Wang, Y. Overexpression of aquaporin-1 aggravates hippocampal damage in mouse traumatic brain injury models. Mol. Med. Rep. 2014, 9, 916–922. [Google Scholar] [CrossRef] [PubMed]
- Tiwari, A.; Dmytriw, A.A.; Bo, R.; Farkas, N.; Ye, P.; Gordon, D.S.; Arcot, K.M.; Turkel-Parrella, D.; Farkas, J. Recurrence and Coniglobus Volumetric Resolution of Subacute and Chronic Subdural Hematoma Post-Middle Meningeal Artery Embolization. Diagnostics 2021, 11, 257. [Google Scholar] [CrossRef] [PubMed]
- Torihashi, K.; Sadamasa, N.; Yoshida, K.; Narumi, O.; Chin, M. Yamagata, SIndependent predictors for recurrence of chronic subdural hematoma: A review of 343 consecutive surgical cases. Neurosurgery 2008, 63, 1125–1129. [Google Scholar] [CrossRef] [PubMed]
- Empitu, M.A.; Ramadhan, R.N.; Rampengan, D.D.C.H. Modulation of AQP2 localization and water reabsorption. J. Physiol. 2024, 602, 1665–1667. [Google Scholar] [CrossRef] [PubMed]
- Wilson, J.L.L.; Miranda, C.A.; Knepper, M.A. Vasopressin and the regulation of aquaporin-2. Clin. Exp. Nephrol. 2013, 17, 751–764. [Google Scholar] [CrossRef] [PubMed]
- Kwon, T.-H.; Frøkiær, J.; Nielsen, S. Regulation of aquaporin-2 in the kidney: A molecular mechanism of body-water homeostasis. Kidney Res. Clin. Pract. 2013, 32, 96–102. [Google Scholar] [CrossRef]
- Gazerani, P. Aquaporins in peripheral nociception. Futur. Neurol. 2017, 12, 1–4. [Google Scholar] [CrossRef]
- Deng, S.; Chen, X.; Lei, Q.; Lu, W. AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage. Front. Immunol. 2022, 13, 847360. [Google Scholar] [CrossRef] [PubMed]
- Jurga, A.M.; Paleczna, M.; Kuter, K.Z. Overview of General and Discriminating Markers of Differential Microglia Phe-notypes. Front. Cell. Neurosci. 2020, 14, 544457. [Google Scholar] [CrossRef]
- Edlmann, E.; Giorgi-Coll, S.; Whitfield, P.C.; Carpenter, K.L.H.; Hutchinson, P.J. Pathophysiology of chronic subdural haematoma: Inflammation, angiogenesis and implications for pharmacotherapy. J. Neuroinflammation 2017, 14, 108. [Google Scholar] [CrossRef] [PubMed]
- Zheng, C.; Wu, D.; Shi, S.; Wang, L. miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury. Ren. Fail. 2021, 43, 291. [Google Scholar] [CrossRef] [PubMed]
- Radin, M.J.; Yu, M.; Stoedkilde, L.; Miller, R.L.; Hoffert, J.D.; Frokiaer, J.; Pisitkun, T.; Knepper, M.A. Aquaporin-2 regulation in health and disease. Vet. Clin. Pathol./Am. Soc. Vet. Clin. Pathol. 2012, 41, 455–470. [Google Scholar] [CrossRef]
- Ando, F. Activation of AQP2 water channels by protein kinase A: Therapeutic strategies for congenital nephrogenic diabetes insipidus. Clin. Exp. Nephrol. 2021, 25, 1051–1056. [Google Scholar] [CrossRef] [PubMed]
- Rieg, T.; Tang, T.; Murray, F.; Schroth, J.; Insel, P.A.; Fenton, R.A.; Hammond, H.K.; Vallon, V. Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla. J. Am. Soc. Nephrol. 2010, 21, 2059–2068. [Google Scholar] [CrossRef] [PubMed]
- Centrone, M.; Ranieri, M.; Di Mise, A.; D’agostino, M.; Venneri, M.; Ferrulli, A.; Valenti, G.; Tamma, G. AQP2 trafficking in health and diseases: An updated overview. Int. J. Biochem. Cell Biol. 2022, 149, 106261. [Google Scholar] [CrossRef]
- Procino, G.; Barbieri, C.; Tamma, G.; De Benedictis, L.; Pessin, J.; Svelto, M.; Valent, G. SNARE Proteins And SNARE Regulators Mediate Aquaporin2 Exocytosis In Renal Cells. FASEB J. 2008, 22, 934.23. [Google Scholar] [CrossRef]
- Blanc, L.; Vidal, M. New insights into the function of Rab GTPases in the context of exosomal secretion. Small GTPases 2018, 9, 95–106. [Google Scholar] [CrossRef]
- Jung, H.J.; Kwon, T.-H. New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus. Kidney Res. Clin. Pract. 2019, 38, 145. [Google Scholar] [CrossRef] [PubMed]
- Hagströmer, C.J.; Steffen, J.H.; Kreida, S.; Al-Jubair, T.; Frick, A.; Gourdon, P.; Törnroth-Horsefield, S. Structural and functional analysis of aquaporin-2 mutants involved in nephrogenic diabetes insipidus. Sci. Rep. 2023, 13, 14674. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Montani, J.-P.; Verrey, F.; Feraille, E.; Ming, X.-F.; Yang, Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption. FASEB J. 2018, 32, 5520–5531. [Google Scholar] [CrossRef] [PubMed]
- Alam, A.; Thelin, E.P.; Tajsic, T.; Khan, D.Z.; Khellaf, A.; Patani, R.; Helmy, A. Cellular infiltration in traumatic brain injury. J. Neuroinflammation 2020, 17, 328. [Google Scholar] [CrossRef]
- Tamma, G.; Valenti, G.; Grossini, E.; Donnini, S.; Marino, A.; Marinelli, R.A.; Calamita, G. Aquaporin Membrane Channels in Oxidative Stress, Cell Signaling, and Aging: Recent Advances and Research Trends. Oxidative Med. Cell. Longev. 2018, 2018, 1501847. [Google Scholar] [CrossRef]
Variable | Total (n = 41) | aSDH Group (n = 21) | cSDH Group (n = 20) | p * |
---|---|---|---|---|
Demographic characteristics | ||||
Age, years | ||||
mean (SD) | 65.9 (14.3) | 58.6 (14.8) | 73.2 (9.4) | <0.0001 |
median (IQR) | 64 (19) | 57 (12) | 74 (9.5) | |
Sex | ||||
male | 31 | 17 | 14 | 0.717 |
female | 10 | 4 | 6 | |
Clinical characteristics | ||||
GCS, median (IQR) | 14 (3) | 12 (9) | 14.5 (2) | 0.005 |
presence of paresis, n | 24 | 15 | 9 | 0.061 |
presence of anisocoria, n | 7 | 7 | 0 | - |
speech impairment, n | 22 | 14 | 8 | 0.121 |
Radiological features, median (IQR) | ||||
hematoma volume, cc | 124.4 (90.2) | 123.4 (84.4) | 125.3 (90.2) | 0.223 |
midline shift, mm | 8.8 (8) | 8.5 (5.7) | 9.5 (6.1) | 0.940 |
hematoma density, HU | 40 (29) | 61 (9) | 32.5 (12) | <0.0001 |
Aquaporin plasma concentration, median (IQR) | ||||
AQP1, ng/mL | 2.81 (0.79) | 2.82 (0.79) | 2.60 (0.91) | 0.494 |
AQP2, ng/mL | 3.60 (1.38) | 3.79 (1.45) | 3.45 (1.21) | 0.452 |
AQP4, ng/mL | 1.39 (0.56) | 1.38 (0.57) | 1.39 (0.45) | 0.847 |
AQP9, ng/mL | 2.47 (0.82) | 2.50 (0.76) | 2.40 (0.68) | 0.452 |
Variable | AQP1 | AQP2 | AQP4 | AQP9 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n | R | p | n | R | p | n | R | p | n | R | p | |
Before surgery | ||||||||||||
Hematoma volume | 21 | −0.327 | 0.148 | 21 | −0.161 | 0.486 | 21 | −0.446 | 0.054 | 21 | −0.326 | 0.149 |
Midline shift | 21 | −0.010 | 0.964 | 21 | −0.196 | 0.395 | 21 | 0.213 | 0.355 | 21 | 0.052 | 0.823 |
15 h post-surgery | ||||||||||||
Hematoma volume | 21 | −0.034 | 0.884 | 21 | −0.104 | 0.654 | 21 | −0.028 | 0.904 | 21 | −0.157 | 0.508 |
Midline shift | 21 | 0.174 | 0.451 | 21 | −0.025 | 0.913 | 21 | 0.093 | 0.690 | 21 | −0.008 | 0.972 |
Post-surgery | ||||||||||||
Hematoma volume | 20 | −0.068 | 0.777 | 21 | 0.209 | 0.364 | 21 | −0.010 | 0.964 | 21 | −0.012 | 0.958 |
Midline shift | 20 | 0.184 | 0.437 | 21 | 0.112 | 0.628 | 21 | 0.068 | 0.770 | 21 | −0.003 | 0.991 |
Change | ||||||||||||
Hematoma volume | 20 | 0.120 | 0.613 | 21 | 0.330 | 0.144 | 21 | −0.130 | 0.575 | 21 | −0.068 | 0.771 |
Midline shift | 20 | −0.036 | 0.880 | 21 | 0.169 | 0.464 | 21 | 0.073 | 0.752 | 21 | 0.130 | 0.574 |
Variable | AQP1 | AQP2 | AQP4 | AQP9 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n | R | p | n | R | p | n | R | p | n | R | p | |
Before surgery | ||||||||||||
Hematoma volume | 20 | 0.023 | 0.925 | 19 | 0.193 | 0.429 | 20 | 0.215 | 0.363 | 19 | 0.158 | 0.519 |
Midline shift | 20 | −0.283 | 0.226 | 19 | −0.540 | 0.017 | 20 | 0.082 | 0.731 | 19 | −0.141 | 0.566 |
15h post-surgery | ||||||||||||
Hematoma volume | 20 | 0.050 | 0.835 | 19 | −0.062 | 0.800 | 20 | −0.213 | 0.368 | 20 | −0.143 | 0.548 |
Midline shift | 20 | 0.056 | 0.814 | 19 | −0.112 | 0.647 | 20 | 0.070 | 0.770 | 20 | 0.049 | 0.837 |
Post-surgery | ||||||||||||
Hematoma volume | 20 | −0.183 | 0.441 | 19 | <0.001 | 1.000 | 20 | −0.237 | 0.315 | 19 | −0.136 | 0.567 |
Midline shift | 20 | 0.106 | 0.656 | 19 | −0.098 | 0.689 | 20 | 0.003 | 0.990 | 20 | 0.330 | 0.156 |
Change | ||||||||||||
Hematoma volume | 19 | −0.168 | 0.491 | 17 | 0.627 | 0.007 | 19 | 0.302 | 0.209 | 18 | 0.391 | 0.108 |
Midline shift | 19 | −0.374 | 0.115 | 17 | 0.174 | 0.505 | 19 | −0.118 | 0.631 | 18 | −0.143 | 0.572 |
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Czyżewski, W.; Korulczyk, J.; Szymoniuk, M.; Sakwa, L.; Litak, J.; Ziemianek, D.; Czyżewska, E.; Mazurek, M.; Kowalczyk, M.; Turek, G.; et al. Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries. Int. J. Mol. Sci. 2024, 25, 6617. https://doi.org/10.3390/ijms25126617
Czyżewski W, Korulczyk J, Szymoniuk M, Sakwa L, Litak J, Ziemianek D, Czyżewska E, Mazurek M, Kowalczyk M, Turek G, et al. Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries. International Journal of Molecular Sciences. 2024; 25(12):6617. https://doi.org/10.3390/ijms25126617
Chicago/Turabian StyleCzyżewski, Wojciech, Jan Korulczyk, Michał Szymoniuk, Leon Sakwa, Jakub Litak, Dominik Ziemianek, Ewa Czyżewska, Marek Mazurek, Michał Kowalczyk, Grzegorz Turek, and et al. 2024. "Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries" International Journal of Molecular Sciences 25, no. 12: 6617. https://doi.org/10.3390/ijms25126617