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The Role of Cx43 in the Survival and Death of Neurons and Glial Cells in Injuries of the Central and Peripheral Nervous System

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Abstract

Connexin 43 (Cx43), a key protein of gap-junctional channels, plays a dual role in regulating the survival and death of neurons and glial cells during injuries to the central (CNS) and peripheral nervous systems (PNS). It supports neuroprotection by maintaining cellular homeostasis but can exacerbate secondary damage by promoting inflammation and apoptosis. This review examines in detail the role of Cx43 in these processes, emphasizing its ambivalent impact, which depends on cell type, injury phase, and molecular microenvironment. Additionally, mechanisms of intercellular communication and prospects for therapeutic modulation of Cx43 to optimize rehabilitation after neurotransmitter are discussed.

About the authors

Ch. D. Nwosu

Research Laboratory "Medical Digital Imaging Based on a Base Model"

Email: chizaramwosu4@gmail.com
Rostov-on-Don, Russia

E. Yu. Kirichenko

Research Laboratory "Medical Digital Imaging Based on a Base Model"

Rostov-on-Don, Russia

A. K. Logvinov

Academy of Biology and Biotechnology, Southern Federal University

Rostov-on-Don, Russia

S. V. Rodkin

Research Laboratory "Medical Digital Imaging Based on a Base Model"

Rostov-on-Don, Russia

References

  1. Smith C. 2023. Traumatic brain injury. In: Neurobiology of Brain Disorders. Elsevier, p. 443–455.
  2. Prins M., Greco T., Alexander D., Giza C.C. 2013. The pathophysiology of traumatic brain injury at a glance. Dis. Model. Mech. 6, 307–315. https://doi.org/10.1242/dmm.011585
  3. Huang C., Han X., Li X., Lam E., Peng W., Lou N., Torres A., Yang M., Garre J.M., Tian G.-F., Bennett M.V.L., Nedergaard M., Takano T. 2012. Critical Role of Connexin 43 in Secondary Expansion of Traumatic Spinal Cord Injury. J. Neurosci. 32, 3333–3338. https://doi.org/10.1523/JNEUROSCI.1216-11.2012
  4. Xie H., Cui Y., Deng F., Feng J. 2015. Connexin: A potential novel target for protecting the central nervous system? Neural Regen. Res. 10, 659. https://doi.org/10.4103/1673-5374.155444
  5. Chandross K.J. 1998. Nerve injury and inflammatory cytokines modulate gap junctions in the peripheral nervous system. Glia. 24, 21–31. https://doi.org/10.1002/(SICI)1098-1136(199809)24:1<21::AID-GLIA3>3.0.CO;2-3
  6. Sirnes S., Kjenseth A., Leithe E., Rivedal E. 2009. Interplay between PKC and the MAP kinase pathway in Connexin43 phosphorylation and inhibition of gap junction intercellular communication. Biochem. Biophys. Res. Commun. 382, 41–45. https://doi.org/10.1016/j.bbrc.2009.02.141
  7. Kim D.Y., Kam Y., Koo S.K., Joe C.O. 1999. Gating Connexin 43 channels reconstituted in lipid vesicles by mitogen-activated protein kinase phosphorylation. J. Biol. Chem. 274, 5581–5587. https://doi.org/10.1074/jbc.274.9.5581
  8. Zhao Y., Rivieccio M.A., Lutz S., Scemes E., Brosnan C.F. 2006. The TLR3 ligand polyI:C downregulates connexin 43 expression and function in astrocytes by a mechanism involving the NF‐κB and PI3 kinase pathways. Glia. 54, 775–785. https://doi.org/10.1002/glia.20418
  9. Sáez J.C., Retamal M.A., Basilio D., Bukauskas F.F., Bennett M.V.L. 2005. Connexin-based gap junction hemichannels: Gating mechanisms. Biochim. Biophys. Acta – Biomembr. 1711, 215–224. https://doi.org/10.1016/j.bbamem.2005.01.014
  10. Ren D., Zheng P., Zou S., Gong Y., Wang Y., Duan J., Deng J., Chen H., Feng J., Zhong C., Chen W. 2022. GJA1-20K enhances mitochondria transfer from astrocytes to neurons via Cx43-TnTs after traumatic brain injury. Cell. Mol. Neurobiol. 42, 1887–1895. https://doi.org/10.1007/s10571-021-01070-x
  11. Lee I.H., Lindqvist E., Kiehn O., Widenfalk J., Olson L. 2005. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury. J. Comp. Neurol. 489, 1–10. https://doi.org/10.1002/cne.20567.
  12. Qi C., Acosta Gutierrez S., Lavriha P., Othman A., Lopez-Pigozzi D., Bayraktar E., Schuster D., Picotti P., Zamboni N., Bortolozzi M., Gervasio F.L., Korkhov V.M. 2023. Structure of the connexin-43 gap junction channel in a putative closed state. Elife. 12, RP87616. https://doi.org/10.7554/eLife.87616.3
  13. Кириченко Е.Ю., Скачков С.Н., Ермаков А.М. 2021. Структура и функции щелевых контактов и составляющих их коннексинов в ЦНС млекопитающих. Биологические мембраны Журнал мембранной и клеточной биологии. 38, 83–97. https://doi.org/10.31857/S0233475521020067
  14. Кириченко Е.Ю., Логвинов А.К., Сехвейл С.М Е.А.М. 2023. Щелевые контакты мозга в норме и при нейроонкогенезе (ультраструктурное исследование) / Донской государственный технический университет. Ростов-на-Дону: ООО «ДГТУ-принт». 180 c.
  15. Nielsen M.S., Nygaard Axelsen L., Sorgen P.L., Verma V., Delmar M., Holstein‐Rathlou N. 2012. Gap Junctions. Compr. Physiol. 2, 1981–2035. https://doi.org/10.1002/j.2040-4603.2012.tb00453.x
  16. Velasco‐Estevez M., Gadalla K.K.E., Liñan‐Barba N., Cobb S., Dev K.K., Sheridan G.K. 2020. Inhibition of Piezo1 attenuates demyelination in the central nervous system. Glia. 68, 356–375. https://doi.org/10.1002/glia.23722
  17. Xiong L.L., Xue L.L., Du R.L., Xu Y., Niu Y.J., Hu Q., Zhou H.L., Liu F., Zhu Z.Q., Yu C.Y., Wang T.H. 2021. LncRNA TCONS_00041002 improves neurological outcomes in neonatal rats with hypoxic-ischemic encephalopathy by inhibiting apoptosis and promoting neuron survival. Exp. Neurol. 346, 113835. https://doi.org/10.1016/j.expneurol.2021.113835
  18. Giorgi C., Baldassari F., Bononi A., Bonora M., De Marchi E., Marchi S., Missiroli S., Patergnani S., Rimessi A., Suski J.M., Wieckowski M.R., Pinton P. 2012. Mitochondrial Ca2+ and apoptosis. Cell Calcium. 52, 36–43. https://doi.org/10.1016/j.ceca.2012.02.008
  19. Li Y.H., Zhang C.L., Zhang X.Y., Zhou H.X., Meng L.L. 2015. Effects of mild induced hypothermia on hippocampal connexin 43 and glutamate transporter 1 expression following traumatic brain injury in rats. Mol. Med. Rep. 11, 1991–1996. https://doi.org/10.3892/mmr.2014.2928
  20. Avila M.A., Sell S.L., Hawkins B.E., Hellmich H.L., Boone D.R., Crookshanks J.M., Prough D.S., DeWitt D.S. 2011. Cerebrovascular connexin expression: Effects of traumatic brain injury. J. Neurotrauma. 28, 1803–1811. https://doi.org/10.1089/neu.2011.1900
  21. Cronin M., Anderson P.N., Cook J.E., Green C.R., Becker D.L. 2008. Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury. Mol. Cell. Neurosci. 39, 152–160. https://doi.org/10.1016/j.mcn.2008.06.005
  22. Chen W., Guo Y., Yang W., Chen L., Ren D., Wu C., He B., Zheng P., Tong W. 2018. Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release. J. Neurophysiol. 119, 305–311. https://doi.org/10.1152/jn.00654.2017
  23. Jaganjac M., Milkovic L., Zarkovic N., Zarkovic K. 2022. Oxidative stress and regeneration. Free Radic. Biol. Med. 181, 154–165. https://doi.org/10.1016/j.freeradbiomed.2022.02.004
  24. Ismail H., Shakkour Z., Tabet M., Abdelhady S., Kobaisi A., Abedi R., Nasrallah L., Pintus G., Al-Dhaheri Y., Mondello S., El-Khoury R., Eid A.H., Kobeissy F., Salameh J. 2020. Traumatic brain injury: Oxidative stress and novel anti-oxidants such as mitoquinone and edaravone. Antioxidants. 9, 943. https://doi.org/10.3390/antiox9100943
  25. Wang C.C., Wee H.Y., Hu C.Y., Chio C.C., Kuo J.R. 2018. The effects of memantine on glutamic receptorassociated nitrosative stress in a traumatic brain injury rat model. World Neurosurg. 112, e719–e731. https://doi.org/10.1016/j.wneu.2018.01.140
  26. Iurlaro R., Muñoz‐Pinedo C. 2016. Cell death induced by endoplasmic reticulum stress. FEBS J. 283, 2640–2652. https://doi.org/10.1111/febs.13598
  27. Muñoz-Ballester C., Leitzel O., Golf S., Phillips C.M., Zeitz M.J., Pandit R., Wash E., Donohue J. V., Smyth J.W., Lamouille S., Robel S. 2025. Astrocytic connexin43 phosphorylation contributes to seizure susceptibility after mild traumatic brain injury. bioRxiv [Preprint]. 2025: 2024.11.12.623104. https://doi.org/10.1101/2024.11.12.623104
  28. Chen M.J., Kress B., Han X., Moll K., Peng W., Ji R., Nedergaard M. 2012. Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia. 60, 1660–1670. https://doi.org/10.1002/glia.22384
  29. Greer K., Chen J., Brickler T., Gourdie R., Theus M.H. 2017. Modulation of gap junction-associated Cx43 in neural stem/progenitor cells following traumatic brain injury. Brain Res. Bull. 134, 38–46. https://doi.org/10.1016/j.brainresbull.2017.06.016
  30. Gaete P.S., Lillo M.A., Figueroa X.F. 2014. Functional role of connexins and pannexins in the interaction between vascular and nervous system. J. Cell. Physiol. 229, 1336–1345. https://doi.org/10.1002/jcp.24563
  31. Chew S.L., Johnson C.S., Green C.R., Danesh-Meyer H. V. 2010. Role of connexin43 in central nervous system injury. Exp. Neurol. 225, 250–261. https://doi.org/10.1016/j.expneurol.2010.07.014
  32. Theodoric N., Bechberger J.F., Naus C.C., Sin W.-C. 2012. Role of Gap junction protein Connexin43 in astrogliosis induced by brain injury. PLoS One. 7, e47311. https://doi.org/10.1371/journal.pone.0047311
  33. Tonkin R.S., Mao Y., O'Carroll S.J., Nicholson L.F., Green C.R., Gorrie C.A., Moalem-Taylor G. 2015. Gap junction proteins and their role in spinal cord injury. Front. Mol. Neurosci. 7, 102. https://doi.org/10.3389/fnmol.2014.00102
  34. Sánchez O.F., Rodríguez A.V., Velasco-España J.M., Murillo L.C., Sutachan J.J., Albarracin S.L. 2020. Role of Connexins 30, 36, and 43 in brain tumors, neurodegenerative diseases, and neuroprotection. Cells. 9, 846. https://doi.org/10.3390/cells9040846
  35. Liang Z., Wang X., Hao Y., Qiu L., Lou Y., Zhang Y., Ma D., Feng J. 2020. The multifaceted role of astrocyte Connexin 43 in ischemic stroke through forming hemichannels and Gap junctions. Front. Neurol. 11, 703. https://doi.org/10.3389/fneur.2020.00703
  36. Orellana J.A., Stehberg J. 2014. Hemichannels: New roles in astroglial function. Front. Physiol. 5, 193. https://doi.org/10.3389/fphys.2014.00193
  37. Cina C., Maass K., Theis M., Willecke K., Bechberger J.F., Naus C.C. 2009. Involvement of the cytoplasmic C-terminal domain of Connexin43 in neuronal migration. J. Neurosci. 29, 2009–2021. https://doi.org/10.1523/JNEUROSCI.5025-08.2009
  38. Rinaldi F., Hartfield E.M., Crompton L.A., Badger J.L., Glover C.P., Kelly C.M., Rosser A.E., Uney J.B., Caldwell M.A. 2014. Cross-regulation of Connexin43 and β-catenin influences differentiation of human neural progenitor cells. Cell Death Dis. 5, e1017–e1017. https://doi.org/10.1038/cddis.2013.546
  39. Chever O., Lee C.Y., Rouach N. 2014. Astroglial Connexin43 hemichannels tune basal excitatory synaptic transmission. J. Neurosci. 34, 11228–11232. https://doi.org/10.1523/JNEUROSCI.0015-14.2014
  40. Retamal M.A., Froger N., Palacios-Prado N., Ezan P., Sáez P.J., Sáez J.C., Giaume C. 2007. Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J. Neurosci. 27, 13781–13792. https://doi.org/10.1523/JNEUROSCI.2042-07.2007
  41. Scemes E., Suadicani S.O., Spray D.C. 2000. Intercellular communication in spinal cord astrocytes: Fine tuning between gap junctions and P2 nucleotide receptors in calcium wave propagation. J. Neurosci. 20, 1435–1445. https://doi.org/10.1523/JNEUROSCI.20-04-01435.2000
  42. Linsambarth S., Carvajal F.J., Moraga-Amaro R., Mendez L., Tamburini G., Jimenez I., Verdugo D.A., Gómez G.I., Jury N., Martínez P., van Zundert B., Varela-Nallar L., Retamal M.A., Martin C., Altenberg G.A., Fiori M.C., Cerpa W., Orellana J.A., Stehberg J. 2022. Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR‐dependent transmission and short‐term fear memory in the basolateral amygdala. FASEB J. 36, e22134. https://doi.org/10.1096/fj.202100798RR
  43. Li K., Zhou H., Zhan L., Shi Z., Sun W., Liu D., Liu L., Liang D., Tan Y., Xu W., Xu E. 2018. Hypoxic preconditioning maintains GLT-1 against transient global cerebral ischemia through upregulating Cx43 and inhibiting c-Src. Front. Mol. Neurosci. 11, 344. https://doi.org/10.3389/fnmol.2018.00344
  44. Rovegno M., Soto P.A., Sáez P.J., Naus C.C., Sáez J.C., von Bernhardi R. 2015. Connexin43 hemichannels mediate secondary cellular damage spread from the trauma zone to distal zones in astrocyte monolayers. Glia. 63, 1185–1199. https://doi.org/10.1002/glia.22808
  45. Scemes E., Spray D.C. 2009. Connexin expression (Gap junctions and hemichannels) in astrocytes. In: Astrocytes in (Patho)Physiology of the Nervous System. Boston, MA: Springer US, pp. 107–150.
  46. McCutcheon S., Spray D.C. 2022. Glioblastoma–astrocyte Connexin 43 Gap junctions promote tumor invasion. Mol. Cancer Res. 20, 319–331. https://doi.org/10.1158/1541-7786.MCR-21-0199
  47. Dong H., Zhou X.W., Wang X., Yang Y., Luo J.W., Liu Y.H., Mao Q. 2017. Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma-associated epileptic discharge. Mol. Med. Rep. 16, 7890–7900. https://doi.org/10.3892/mmr.2017.7618
  48. Kirichenko E.Y., Salah M.S., Goncharova Z.A., Nikitin A.G., Filippova S.Y., Todorov S.S., Akimenko M.A., Logvinov A.K. 2020. Ultrastructural evidence for presenсe of gap junctions in rare case of pleomorphic xanthoastrocytoma. Ultrastruct. Pathol. 44, 227–236. https://doi.org/10.1080/01913123.2020.1737609
  49. Zhang M., Wang Z.Z., Chen N.H. 2023. Connexin 43 phosphorylation: Implications in multiple diseases. Molecules. 28, 4914. https://doi.org/10.3390/molecules28134914
  50. Liao C.K., Cheng H.H., Wang S.D., Yeih D.F., Wang S.M. 2013. PKCɛ mediates serine phosphorylation of connexin43 induced by lysophosphatidylcholine in neonatal rat cardiomyocytes. Toxicology. 314, 11–21. https://doi.org/10.1016/j.tox.2013.08.001
  51. Strauss R.E., Gourdie R.G. 2020. Cx43 and the actin cytoskeleton: Novel roles and implications for cell-cell junction-based barrier function regulation. Biomolecules. 10, 1656. https://doi.org/10.3390/biom10121656
  52. Neumann E., Hermanns H., Barthel F., Werdehausen R., Brandenburger T. 2015. Expression changes of MicroRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats. Mol. Pain. 11, 39. https://doi.org/10.1186/s12990-015-0045-y
  53. El-Gazar A.A., El-Emam S.Z., M. El-Sayyad S., ElMancy S.S., Fayez S.M., Sheta N.M., Al-Mokaddem A.K., Ragab G.M. 2024. Pegylated polymeric micelles of boswellic acid-selenium mitigates repetitive mild traumatic brain injury: Regulation of miR-155 and miR-146a/BDNF/Klotho/Foxo3a cue. Int. Immunopharmacol. 134, 112118. https://doi.org/10.1016/j.intimp.2024.112118
  54. Sun L.Q., Gao J.L., Cui Y., Zhao M.M., Jing X. Bin, Li R., Tian Y.X., Cui J.Z., Wu Z.X. 2015. Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats. Mol. Med. Rep. 11, 4419–4423. https://doi.org/10.3892/mmr.2015.3264
  55. Feng J., Zou S., Yang X., Wang Z., Jiang B., Hou T., Duan J., Hong T., Chen W. 2023. Astrocyte-derived exosome-transported GJA1-20k attenuates traumatic brain injury in rats. Chin. Med. J. (Engl). 136, 880–882. https://doi.org/10.1097/CM9.0000000000002320
  56. Zhang L., Xiao Z., Su Z., Wang X., Tian H., Su M. 2024. Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop. J. Orthop. Surg. Res. 19, 387. https://doi.org/10.1186/s13018-024-04879-6
  57. Chen B., Sun L., Wu X., Ma J. 2017. Correlation between connexin and traumatic brain injury in patients. Brain Behav. 7, 112404. https://doi.org/10.1002/brb3.770
  58. Xia J., Tan Y., Mao C., Shen W., Zhao Y. 2024. Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury by regulating the Cx43. Exp. Gerontol. 189, 112404. https://doi.org/10.1016/j.exger.2024.112404
  59. Zhang T., Wang Y., Xia Q., Tu Z., Sun J., Jing Q., Chen P., Zhao X. 2021. Propofol mediated protection of the brain from ischemia/reperfusion injury through the regulation of microglial Connexin 43. Front. Cell Dev. Biol. 9. https://doi.org/10.3389/fcell.2021.637233
  60. Yan J., Xie S., Chen D., Xiao J., Zeng E., Hong T., Duan J. 2025. Role ofCx43; and ACKR3 in modulating astrocytic response and neuronal survival post‐subarachnoid hemorrhage. Glia. 35, 677–682. https://doi.org/10.1002/glia.70008
  61. Sun L., Gao J., Zhao M., Jing X., Cui Y., Xu X., Wang K., Zhang W., Cui J. 2014. The effects of BMSCs transplantation on autophagy by CX43 in the hippocampus following traumatic brain injury in rats. Neurol. Sci. 35, 677–682. https://doi.org/10.1007/s10072-013-1575-6
  62. Zheng P., Ren D., Yu C., Zhang X., Zhang Y. 2022. DNA Methylation-related circRNA_0116449 Is Involved in lipid peroxidation in ttraumatic brain injury. Front. Mol. Neurosci. 15, 904913. https://doi.org/10.3389/fnmol.2022.904913
  63. Greer K., Basso E.K.G., Kelly C., Cash A., Kowalski E., Cerna S., Ocampo C.T., Wang X., Theus M.H. 2020. Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBIinduced learning and memory impairments. Sci. Rep. 10, 15374. https://doi.org/10.1038/s41598-020-72380-1
  64. Wu F., Liang T., Liu Y., Sun Y., Wang B. 2024. Hydrogen mitigates brain injury by prompting NEDD4-CX43- mediated mitophagy in traumatic brain injury. Exp. Neurol. 379, 114876. https://doi.org/10.1016/j.expneurol.2024.114876
  65. Yu B., Ma H., Kong L., Shi Y., Liu Y. 2013. Experimental research enhanced connexin 43 expression following neural stem cell transplantation in a rat model of traumatic brain injury. Arch. Med. Sci. 1, 132–138. https://doi.org/10.5114/aoms.2012.31438
  66. Chen X., Liang H., Xi Z., Yang Y., Shan H., Wang B., Zhong Z., Xu C., Yang G.Y., Sun Q., Sun Y., Bian L. 2020. BM-MSC Transplantation alleviates intracerebral hemorrhage-induced brain injury, promotes astrocytes Vimentin expression, and enhances astrocytes antioxidation via the Cx43/Nrf2/HO-1 Axis. Front. Cell Dev. Biol. 8, 302. https://doi.org/10.3389/fcell.2020.00302
  67. Нвосу Ч.Д., Кириченко Е.Ю., Родькин С.В. 2025. Экспрессия cx43 в нервной ткани при тяжелой. черепно-мозговой травме. Рецепторы и внутриклеточная сигнализация. 1, 310–315.
  68. DeWitt D.S., Prough D.S. 2003. Traumatic cerebral vascular injury: The effects of concussive brain injury on the cerebral vasculature. J. Neurotrauma. 20, 795–825. https://doi.org/10.1089/089771503322385755
  69. Smith M., Wilkinson S. 2017. ER homeostasis and autophagy. Essays Biochem. 61, 625–635. https://doi.org/10.1042/EBC20170092
  70. Schwarzmaier S.M., Kim S.W., Trabold R., Plesnila N. 2010. Temporal Profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice. J. Neurotrauma. 27, 121–130. https://doi.org/10.1089/neu.2009.1114
  71. Bains M., Hall E.D. 2012. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim. Biophys. Acta – Mol. Basis Dis. 1822, 675–684. https://doi.org/10.1016/j.bbadis.2011.10.017
  72. O’Carroll S.J., Gorrie C.A., Velamoor S., Green C.R., Nicholson L.F.B. 2013. Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury. Neurosci. Res. 75, 256–267. https://doi.org/10.1016/j.neures.2013.01.004
  73. Abou-Mrad Z., Alomari S.O., Bsat S., Moussalem C.K., Alok K., El Houshiemy M.N., Alomari A.O., Minassian G.B., Omeis I.A. 2020. Role of connexins in spinal cord injury: An update. Clin. Neurol. Neurosurg. 197, 106102. https://doi.org/10.1016/j.clineuro.2020.106102
  74. Mao Y., Tonkin R.S., Nguyen T., O’Carroll S.J., Nicholson L.F.B., Green C.R., Moalem-Taylor G., Gorrie C.A. 2017. Systemic administration of Connexin43 mimetic peptide improves functional recovery after traumatic spinal cord injury in adult rats. J. Neurotrauma. 34, 707–719. https://doi.org/10.1089/neu.2016.4625
  75. O’Carroll S.J., Alkadhi M., Nicholson L.F.B., Green C.R. 2008. Connexin43 mimetic peptides reduce swelling, astrogliosis, and neuronal cell death after spinal cord injury. Cell Commun. Adhes. 15, 27–42. https://doi.org/10.1080/15419060802014164
  76. Choi S.R., Roh D.H., Yoon S.Y., Kwon S.G., Choi H.S., Han H.J., Beitz A.J., Lee J.H. 2016. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice. Neuropharmacology. 111, 34–46. https://doi.org/10.1016/j.neuropharm.2016.08.027
  77. Zhang C., Yan Z., Maknojia A., Riquelme M.A., Gu S., Booher G., Wallace D.J., Bartanusz V., Goswami A., Xiong W., Zhang N., Mader M.J., An Z., Sayre N.L., Jiang J.X. 2021. Inhibition of astrocyte hemichannel improves recovery from spinal cord injury. JCI Insight. 6. https://doi.org/10.1172/jci.insight.134611
  78. Chen G., Park C.K., Xie R.G., Berta T., Nedergaard M., Ji R.R. 2014. Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice. Brain. 137, 2193–2209. https://doi.org/10.1093/brain/awu140
  79. Xu Q., Cheong Y.K., He S.Q., Tiwari V., Liu J., Wang Y., Raja S.N., Li J., Guan Y., Li W. 2014. Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury. Neurosci. Lett. 566, 194–199. https://doi.org/10.1016/j.neulet.2014.03.004
  80. Meier C., Rosenkranz K. 2014. Cx43 expression and function in the nervous system – implications for stem cell mediated regeneration. Front. Physiol. 5, 1163436. https://doi.org/10.3389/fphys.2014.00106
  81. Huang Q., Sha W., Gu Q., Wang J., Zhu Y., Xu T., Xu Z., Yan F., Lin X., Tian S. 2023. Inhibition of Connexin43 improves the recovery of spinal cord injury against ferroptosis via the SLC7A11/GPX4 Pathway. Neuroscience. 526, 121–134. https://doi.org/10.1016/j.neuroscience.2023.06.017
  82. Fabbiani G., Reali C., Valentín-Kahan A., Rehermann M.I., Fagetti J., Falco M.V., Russo R.E. 2020. Connexin signaling is involved in the reactivation of a latent stem cell niche after spinal cord injury. J. Neurosci. 40, 2246–2258. https://doi.org/10.1523/JNEUROSCI.2056-19.2020
  83. Toro C.A., De Gasperi R., Vanselow K., Harlow L., Johnson K., Aslan A., Bauman W.A., Cardozo C.P., Graham Z.A. 2024. Muscle-restricted knockout of connexin 43 and connexin 45 accelerates and improves locomotor recovery after contusion spinal cord injury. Front. Physiol. 15, 194–199. https://doi.org/10.3389/fphys.2024.1486691
  84. Zhang D., Qin C., Meng F., Han X., Guo X. 2024. N‐Acetylcysteine treats spinal cord injury by inhibiting astrocyte proliferation. Anal. Cell. Pathol. (Amst.) 2024, 6624283. https://doi.org/10.1155/2024/6624283
  85. Toro C.A., Johnson K., Hansen J., Siddiq M.M., Vásquez W., Zhao W., Graham Z.A., Sáez J.C., Iyengar R., Cardozo C.P. 2023. Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury. Front. Cell. Neurosci. 17, 1104–1119. https://doi.org/10.3389/fncel.2023.1163436
  86. Huang J., Hu X., Chen Z., Ouyang F., Li J., Hu Y., Zhao Y., Wang J., Yao F., Jing J., Cheng L. 2024. Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord. J. Neuroinflammation. 21, 88. https://doi.org/10.1186/s12974-024-03089-5
  87. Zou J., Guo Y., Wei L., Yu F., Yu B., Xu A. 2020. Long noncoding RNA POU3F3 and α-synuclein in plasma L1CAM exosomes combined with β-glucocerebrosidase activity: Potential predictors of Parkinson’s disease. Neurotherapeutics. 17, 1104–1119. https://doi.org/10.1007/s13311-020-00842-5
  88. Pierce J.D., Gupte R., Thimmesch A., Shen Q., Hiebert J.B., Brooks W.M., Clancy R.L., Diaz F.J., Harris J.L. 2018. Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism. J. Neurosci. Res. 96, 1080–1092. https://doi.org/10.1002/jnr.24210
  89. Liu P., Anandhan A., Chen J., Shakya A., Dodson M., Ooi A., Chapman E., White E., Garcia J.G., Zhang D.D. 2023. Decreased autophagosome biogenesis, reduced NRF2, and enhanced ferroptotic cell death are underlying molecular mechanisms of nonalcoholic fatty liver disease. Redox Biol. 59, 102570. https://doi.org/10.1016/j.redox.2022.102570
  90. Wang A., Xu C. 2019. The role of connexin43 in neuropathic pain induced by spinal cord injury. Acta Biochim. Biophys. Sin. (Shanghai). 51, 554–560. https://doi.org/10.1093/abbs/gmz038
  91. Chandross K.J., Kessler J.A., Cohen R.I., Simburger E., Spray D.C., Bieri P., Dermietzel R. 1996. Altered Connexin expression after peripheral nerve injury. Mol. Cell. Neurosci. 7, 501–518. https://doi.org/10.1006/mcne.1996.0036
  92. Xing J., Wang Η., Chen L., Wang H., Huang H., Huang J., Xu C. 2023. Blocking Cx43 alleviates neuropathic pain in rats with chronic constriction injury via the P2X4 and P38/ERK-P65 pathways. Int. Immunopharmacol. 114, 109506. https://doi.org/10.1016/j.intimp.2022.109506
  93. Yoshimura T., Satake M., Kobayashi T. 1996. Connexin43 is another Gap junction protein in the peripheral nervous system. J. Neurochem. 67, 1252–1258. https://doi.org/10.1046/j.1471-4159.1996.67031252.x
  94. Wong C.E., Liu W., Huang C.C., Lee P.H., Huang H.W., Chang Y., Lo H.T., Chen H.F., Kuo L.C., Lee J.S. 2024. Sciatic nerve stimulation alleviates neuropathic pain and associated neuroinflammation in the dorsal root ganglia in a rodent model. J. Transl. Med. 22, 770. https://doi.org/10.1186/s12967-024-05573-1
  95. Zhou L., Ao L., Yan Y., Li C., Li W., Ye A., Liu J., Hu Y., Fang W., Li Y. 2020. Levo-corydalmine attenuates vincristine-induced neuropathic pain in mice by upregulating the Nrf2/HO-1/CO pathway to inhibit Connexin 43 expression. Neurotherapeutics. 17, 340–355. https://doi.org/10.1007/s13311-019-00784-7
  96. Burrell J.C., Vu P.T., Alcott O.J.B., Toro C.A., Cardozo C., Cullen D.K. 2023. Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair. Front. Cell. Neurosci. 17, 1240916. https://doi.org/10.3389/fncel.2023.1240916
  97. Ohsumi A., Nawashiro H., Otani N., Ooigawa H., Toyooka T., Shima K. 2010. Temporal and spatial profile of phosphorylated Connexin43 after traumatic brain injury in rats. J. Neurotrauma. 27, 1255–1263. https://doi.org/10.1089/neu.2009.1234
  98. Bretová K., Svobodová V., Dubový P. 2024. Changes in Cx43 and AQP4 proteins, and the capture of 3 kDa dextran in subpial astrocytes of the rat medial prefrontal cortex after both sham surgery and sciatic nerve injury. Int. J. Mol. Sci. 25, 10989. https://doi.org/10.3390/ijms252010989
  99. Hu X., Liu Y., Wu J., Liu Y., Liu W., Chen J., Yang F. 2020. Inhibition of P2X7R in the amygdala ameliorates symptoms of neuropathic pain after spared nerve injury in rats. Brain. Behav. Immun. 88, 507–514. https://doi.org/10.1016/j.bbi.2020.04.030
  100. Kuebart A., Wollborn V., Huhn R., Hermanns H., Werdehausen R., Brandenburger T. 2020. Intraneural application of microRNA-1 mimetic nucleotides does not resolve neuropathic pain after chronic constriction injury in rats. J. Pain Res. 3, 2907–2914. https://doi.org/10.2147/JPR.S266937
  101. Konnova E.A., Deftu A.F., Chu Sin Chung P., Pertin M., Kirschmann G., Decosterd I., Suter M.R. 2023. Characterisation of GFAP-Expressing glial cells in the dorsal root ganglion after spared nerve injury. Int. J. Mol. Sci. 24, 15559. https://doi.org/10.3390/ijms242115559
  102. Dennis E.L., Baron D., Bartnik‐Olson B., Caeyenberghs K., Esopenko C., Hillary F.G., Kenney K., Koerte I.K., Lin A.P., Mayer A.R., Mondello S., Olsen A., Thompson P.M., Tate D.F., Wilde E.A. 2022. ENIGMA brain injury: Framework, challenges, and opportunities. Hum. Brain Mapp. 43, 149–166. https://doi.org/10.1002/hbm.25046
  103. Nakase T., Naus C.C.G. 2004. Gap junctions and neurological disorders of the central nervous system. Biochim. Biophys. Acta – Biomembr. 1662, 149–158. https://doi.org/10.1016/j.bbamem.2004.01.009
  104. Uzu M., Sin W., Shimizu A., Sato H. 2018. Conflicting roles of Connexin43 in tumor invasion and growth in the central nervous system. Int. J. Mol. Sci. 19, 1159. https://doi.org/10.3390/ijms19041159

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