Skip to main content

Advertisement

SpringerLink
Log in

The effects of Na+-K+-2Cl− cotransporter inhibition on passive avoidance learning and memory deficit in a rat model of traumatic brain injury

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Abstract

Traumatic brain injury (TBI) is one of the leading causes of death, long-term disability, and neurological impairments in children and young adults. TBI is associated with cognitive deficits and memory impairment. The Na+-K+-2Cl (NKCC) cotransporter contributes to the pathophysiology of common neurological disorders following TBI. The present study was designed to explore the potential therapeutic effect of bumetanide (a relatively specific inhibitor of NKCC1) on TBI-induced passive avoidance learning deficit in a rat model of controlled cortical impact (CCI) injury. Male rats were randomly divided into the following groups: (i) control animals that have undergone a sham surgical procedure, except for CCI delivery, (ii) TBI; received CCI delivery, (iii) Bumetanide plus TBI; received bumetanide 30 min before CCI delivery, (iv) TBI plus bumetanide; received bumetanide 30 min after CCI delivery. Passive avoidance learning (PAL) was assessed using a step-through apparatus on day 8 after TBI induction. CCI resulted in PAL deficits. The step-through latency in the acquisition trial (STLa) was significantly higher in the injured animals, and both pre-CCI and post-CCI bumetanide treatment decreased STLa. A decrease in step-through latency in the retention trial (STLr) and an increase in time spent in the dark compartment (TDC) during the retention test was observed in the injured animals. Both pre-CCI and post-CCI bumetanide treatment increased STLr and decreased TDC in injured animals. These findings suggest that bumetanide has a neuroprotective effect on TBI-induced memory impairment in rats and pharmacological inhibition of NKCC1 is protective against brain injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data are available for any scientific use with kind permission.

References

  1. Badhiwala JH, Wilson JR, Fehlings MG. Global burden of traumatic brain and spinal cord injury. The Lancet Neurology. 2019;18(1):24-5.

    Article  PubMed  Google Scholar 

  2. Cristofori I, Levin HS. Traumatic brain injury and cognition. Handbook of clinical neurology. 128: Elsevier; 2015. p. 579–611.

  3. Gupta R, Sen N. Traumatic brain injury: a risk factor for neurodegenerative diseases. Reviews in the Neurosciences. 2016;27(1):93-100.

    Article  PubMed  Google Scholar 

  4. Prins M, Greco T, Alexander D, Giza CC. The pathophysiology of traumatic brain injury at a glance. Disease models & mechanisms. 2013;6(6):1307-15.

    CAS  Google Scholar 

  5. MacFarlane MP, Glenn TC. Neurochemical cascade of concussion. Brain injury. 2015;29(2):139-53.

    Article  PubMed  Google Scholar 

  6. Kaur P, Sharma S. Recent advances in pathophysiology of traumatic brain injury. Current neuropharmacology. 2018;16(8):1224-38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gupta RK, Prasad S. Age-dependent alterations in the interactions of NF-κB and N-myc with GLT-1/EAAT2 promoter in the pericontusional cortex of mice subjected to traumatic brain injury. Molecular Neurobiology. 2016;53(5):3377-88.

    Article  CAS  PubMed  Google Scholar 

  8. Gupta R, Prasad S. Early down regulation of the glial Kir4. 1 and GLT-1 expression in pericontusional cortex of the old male mice subjected to traumatic brain injury. Biogerontology. 2013;14(5):531–41.

  9. Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery. 1996;38(6):1176-95.

    CAS  PubMed  Google Scholar 

  10. Sullivan PG, Keller JN, Mattson MP, Scheff SW. Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function. Journal of neurotrauma. 1998;15(10):789-98.

    Article  CAS  PubMed  Google Scholar 

  11. D’Ambrosio R, Maris DO, Grady MS, Winn HR, Janigro D. Impaired K+ homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia. Journal of Neuroscience. 1999;19(18):8152-62.

    Article  PubMed  Google Scholar 

  12. Vitvitsky VM, Garg SK, Keep RF, Albin RL, Banerjee R. Na+ and K+ ion imbalances in Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2012;1822(11):1671–81.

  13. Haas M, Forbush III B. The Na-K-Cl cotransporter of secretory epithelia. Annual review of physiology. 2000;62(1):515-34.

    Article  CAS  PubMed  Google Scholar 

  14. Plotkin M, Kaplan M, Peterson L, Gullans S, Hebert S, Delpire E. Expression of the Na (+)-K (+)-2Cl-cotransporter BSC2 in the nervous system. American Journal of Physiology-Cell Physiology. 1997;272(1):C173-C83.

    Article  CAS  Google Scholar 

  15. Chen H, Sun D. The role of Na–K–Cl co–transporter in cerebral ischemia. Neurological research. 2005;27(3):280-6.

    Article  CAS  PubMed  Google Scholar 

  16. Chen H, Luo J, Kintner DB, Shull GE, Sun D. Na+-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism. 2005;25(1):54-66.

    Article  Google Scholar 

  17. Lu K-T, Wu C-Y, Cheng N-C, Wo Y-YP, Yang J-T, Yen H-H, et al. Inhibition of the Na+–K+–2Cl−-cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage. European journal of pharmacology. 2006;548(1–3):99–105.

  18. Cong D, Zhu W, S Kuo J, Hu S, Sun D. Ion transporters in brain tumors. Current medicinal chemistry. 2015;22(10):1171–81.

  19. Castrop H, Schießl IM. Physiology and pathophysiology of the renal Na-K-2Cl cotransporter (NKCC2). American Journal of Physiology-Renal Physiology. 2014;307(9):F991-F1002.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang J, Pu H, Zhang H, Wei Z, Jiang X, Xu M, et al. Inhibition of Na+-K+-2Cl− cotransporter attenuates blood-brain-barrier disruption in a mouse model of traumatic brain injury. Neurochemistry International. 2017;111:23-31.

    Article  CAS  PubMed  Google Scholar 

  21. Lu K-T, Cheng N-C, Wu C-Y, Yang Y-L. NKCC1-mediated traumatic brain injury-induced brain edema and neuron death via Raf/MEK/MAPK cascade. Critical care medicine. 2008;36(3):917-22.

    Article  CAS  PubMed  Google Scholar 

  22. Lu K-T, Wu C-Y, Yen H-H, Peng J-HF, Wang C-L, Yang Y-L. Bumetanide administration attenuated traumatic brain injury through IL-1 overexpression. Neurological research. 2007;29(4):404–9.

  23. O'donnell ME, Tran L, Lam TI, Liu XB, Anderson SE. Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke. Journal of Cerebral Blood Flow & Metabolism. 2004;24(9):1046–56.

  24. Yan Y, Dempsey RJ, Flemmer A, Forbush B, Sun D. Inhibition of Na+–K+–Cl− cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain research. 2003;961(1):22-31.

    Article  CAS  PubMed  Google Scholar 

  25. Liu S, Jia F, Xia T, Xu N, Zhang Y, Jiang H. Cognitive dysfunction and bumetanide treatment in a valproate-induced rat model of autism. Int J Clin Exp Med. 2016;9(12):23363-74.

    CAS  Google Scholar 

  26. Gharaylou Z, Shafaghi L, Oghabian MA, Yoonessi A, Tafakhori A, Shahsavand Ananloo E, et al. Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy. Frontiers in neurology. 2019;10:483.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Stevens RA, Butler BD, Kokane SS, Womack AW, Lin Q. Neonatal inhibition of Na+-K+-2Cl−-cotransporter prevents ketamine induced spatial learning and memory impairments. Neurotoxicology and teratology. 2017;60:82-6.

    Article  CAS  PubMed  Google Scholar 

  28. Goubert E, Altvater M, Rovira M-N, Khalilov I, Mazzarino M, Sebastiani A, et al. Bumetanide prevents brain trauma-induced depressive-like behavior. Frontiers in molecular neuroscience. 2019;12:12.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ben-Ari Y. NKCC1 chloride importer antagonists attenuate many neurological and psychiatric disorders. Trends in neurosciences. 2017;40(9):536-54.

    Article  CAS  PubMed  Google Scholar 

  30. Xu W-s, Sun X, Song C-g, Mu X-p, Ma W-p, Zhang X-h, et al. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia. Neural regeneration research. 2016;11(5):745.

  31. Damier P, Hammond C, Ben-Ari Y. Bumetanide to treat Parkinson disease: a report of 4 cases. Clinical neuropharmacology. 2016;39(1):57-9.

    Article  PubMed  Google Scholar 

  32. Lemonnier E, Robin G, Degrez C, Tyzio R, Grandgeorge M, Ben‐Ari Y. Treating F ragile X syndrome with the diuretic bumetanide: A case report. Acta Paediatrica. 2013;102(6):e288-e90.

    Article  PubMed  Google Scholar 

  33. Lemonnier E, Lazartigues A, Ben-Ari Y. Treating schizophrenia with the diuretic bumetanide: a case report. Clinical neuropharmacology. 2016;39(2):115-7.

    Article  PubMed  Google Scholar 

  34. Hall ED, Bryant YD, Cho W, Sullivan PG. Evolution of post-traumatic neurodegeneration after controlled cortical impact traumatic brain injury in mice and rats as assessed by the de Olmos silver and fluorojade staining methods. Journal of neurotrauma. 2008;25(3):235-47.

    Article  PubMed  Google Scholar 

  35. Rashno M, Sarkaki A, Farbood Y, Rashno M, Khorsandi L, Naseri MKG, et al. Therapeutic effects of chrysin in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study. Life sciences. 2019;228:285-94.

    Article  CAS  PubMed  Google Scholar 

  36. Malkesman O, Tucker LB, Ozl J, McCabe JT. Traumatic brain injury–modeling neuropsychiatric symptoms in rodents. Frontiers in neurology. 2013;4:157.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Jayakumar AR, Panickar KS, Curtis KM, Tong XY, Moriyama M, Norenberg MD. Na‐K‐Cl cotransporter‐1 in the mechanism of cell swelling in cultured astrocytes after fluid percussion injury. Journal of neurochemistry. 2011;117(3):437-48.

    Article  CAS  PubMed  Google Scholar 

  38. Donkin JJ, Vink R. Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Current opinion in neurology. 2010;23(3):293-9.

    Article  CAS  PubMed  Google Scholar 

  39. Yan EB, Satgunaseelan L, Paul E, Bye N, Nguyen P, Agyapomaa D, et al. Post-traumatic hypoxia is associated with prolonged cerebral cytokine production, higher serum biomarker levels, and poor outcome in patients with severe traumatic brain injury. Journal of neurotrauma. 2014;31(7):618-29.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Salvador E, Burek M, Förster CY. Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade. Frontiers in cellular neuroscience. 2015;9:323.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Weber JT. Altered calcium signaling following traumatic brain injury. Frontiers in pharmacology. 2012;3:60.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yi J-H, Hazell AS. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochemistry international. 2006;48(5):394-403.

    Article  CAS  PubMed  Google Scholar 

  43. Ezza H, Khadrawyb Y. Glutamate excitotoxicity and neurodegeneration. J Mol Genet Med. 2014;8(4):141.

    Google Scholar 

  44. Kornbuber J, Wiltfang J. The role of glutamate in dementia. Ageing and Dementia: Springer; 1998. p. 277-87.

    Google Scholar 

  45. Esposito Z, Belli L, Toniolo S, Sancesario G, Bianconi C, Martorana A. Amyloid β, glutamate, excitotoxicity in Alzheimer's disease: are we on the right track? CNS neuroscience & therapeutics. 2013;19(8):549-55.

    Article  CAS  Google Scholar 

  46. Beck J, Lenart B, Kintner DB, Sun D. Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity. Journal of Neuroscience. 2003;23(12):5061-8.

    Article  CAS  PubMed  Google Scholar 

  47. Wong J, Hoe NW, Zhiwei F, Ng I. Apoptosis and traumatic brain injury. Neurocritical care. 2005;3(2):177-82.

    Article  CAS  PubMed  Google Scholar 

  48. Maiti P, Singh SB, Mallick B, Muthuraju S, Ilavazhagan G. High altitude memory impairment is due to neuronal apoptosis in hippocampus, cortex and striatum. Journal of chemical neuroanatomy. 2008;36(3-4):227-38.

    Article  CAS  PubMed  Google Scholar 

  49. Hui H, Rao W, Zhang L, Xie Z, Peng C, Su N, et al. Inhibition of Na+-K+-2Cl-cotransporter-1 attenuates traumatic brain injury-induced neuronal apoptosis via regulation of Erk signaling. Neurochemistry international. 2016;94:23-31.

    Article  CAS  PubMed  Google Scholar 

  50. Allison DJ, Ditor DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. Journal of neuroinflammation. 2014;11(1):1-12.

    Article  Google Scholar 

  51. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nature Reviews Neuroscience. 2003;4(4):299-309.

    Article  CAS  PubMed  Google Scholar 

  52. Shulga A, Magalhães AC, Autio H, Plantman S, di Lieto A, Nykjær A, et al. The loop diuretic bumetanide blocks posttraumatic p75NTR upregulation and rescues injured neurons. Journal of Neuroscience. 2012;32(5):1757-70.

    Article  CAS  PubMed  Google Scholar 

  53. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annual review of neuroscience. 2001;24(1):677-736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sandhya VK, Raju R, Verma R, Advani J, Sharma R, Radhakrishnan A, et al. A network map of BDNF/TRKB and BDNF/p75NTR signaling system. Journal of cell communication and signaling. 2013;7(4):301-7.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Brito V, Giralt A, Enriquez-Barreto L, Puigdellívol M, Suelves N, Zamora-Moratalla A, et al. Neurotrophin receptor p75 NTR mediates Huntington’s disease–associated synaptic and memory dysfunction. The Journal of clinical investigation. 2014;124(10):4411-28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Choucry AM, Al-Shorbagy MY, Attia AS, El-Abhar HS. Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats. Journal of Molecular Neuroscience. 2019;68(1):78-90.

    Article  CAS  PubMed  Google Scholar 

  57. Xu W, Mu X, Wang H, Song C, Ma W, Jolkkonen J, et al. Chloride co-transporter NKCC1 inhibitor bumetanide enhances neurogenesis and behavioral recovery in rats after experimental stroke. Molecular neurobiology. 2017;54(4):2406-14.

    Article  CAS  PubMed  Google Scholar 

  58. Rola R, Mizumatsu S, Otsuka S, Morhardt DR, Noble-Haeusslein LJ, Fishman K, et al. Alterations in hippocampal neurogenesis following traumatic brain injury in mice. Experimental neurology. 2006;202(1):189-99.

    Article  CAS  PubMed  Google Scholar 

  59. Feng Y, Cui Y, Gao JL, Li R, Jiang XH, Tian YX, et al. Neuroprotective effects of resveratrol against traumatic brain injury in rats: involvement of synaptic proteins and neuronal autophagy. Molecular medicine reports. 2016;13(6):5248-54.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang M, Shan H, Chang P, Wang T, Dong W, Chen X, et al. Hydrogen sulfide offers neuroprotection on traumatic brain injury in parallel with reduced apoptosis and autophagy in mice. PloS one. 2014;9(1):e87241.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Wang Z-f, Gao C, Chen W, Gao Y, Wang H-c, Meng Y, et al. Salubrinal offers neuroprotection through suppressing endoplasmic reticulum stress, autophagy and apoptosis in a mouse traumatic brain injury model. Neurobiology of learning and memory. 2019;161:12–25.

  62. Sun L, Zhao M, Liu M, Su P, Zhang J, Li Y, et al. Suppression of FoxO3a attenuates neurobehavioral deficits after traumatic brain injury through inhibiting neuronal autophagy. Behavioural brain research. 2018;337:271-9.

    Article  CAS  PubMed  Google Scholar 

  63. Xu Y, Tian Y, Tian Y, Li X, Zhao P. Autophagy activation involved in hypoxic‐ischemic brain injury induces cognitive and memory impairment in neonatal rats. Journal of neurochemistry. 2016;139(5):795-805.

    Article  CAS  PubMed  Google Scholar 

  64. Luo C-L, Li B-X, Li Q-Q, Chen X-P, Sun Y-X, Bao H-J, et al. Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience. 2011;184:54-63.

    Article  CAS  PubMed  Google Scholar 

  65. Hung C-M, Peng C-K, Wu C-P, Huang K-L. Bumetanide attenuates acute lung injury by suppressing macrophage activation. Biochemical pharmacology. 2018;156:60-7.

    Article  CAS  PubMed  Google Scholar 

  66. Zhang Y-B, Li S-X, Chen X-P, Yang L, Zhang Y-G, Liu R, et al. Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neuroscience bulletin. 2008;24(3):143-9.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Mu X, Wang H, Cheng X, Yang L, Sun X, Qu H, et al. Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats. Neuroscience. 2017;365:83-93.

    Article  CAS  PubMed  Google Scholar 

  68. Lam TI, Anderson SE, Glaser N, O’Donnell ME. Bumetanide reduces cerebral edema formation in rats with diabetic ketoacidosis. Diabetes. 2005;54(2):510-6.

    Article  CAS  PubMed  Google Scholar 

  69. Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. Journal of neuroscience methods. 1991;39(3):253-62.

    Article  CAS  PubMed  Google Scholar 

  70. Karimi SA, Hosseinmardi N, Janahmadi M, Sayyah M, Hajisoltani R. The protective effect of hydrogen sulfide (H 2 S) on traumatic brain injury (TBI) induced memory deficits in rats. Brain Research Bulletin. 2017.

  71. Karimi SA, Hosseinmardi N, Sayyah M, Hajisoltani R, Janahmadi M. Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (Ih) in hippocampal CA1 neurons in a rat model of traumatic brain injury. Hippocampus. 2020.

  72. Karimi SA, Hosseinmardi N, Sayyah M, Hajisoltani R, Janahmadi M. Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (Ih) in hippocampal CA1 neurons in a rat model of traumatic brain injury. Hippocampus. 2021;31(2):156-69.

    Article  CAS  PubMed  Google Scholar 

  73. Taylor AN, Rahman SU, Sanders NC, Tio DL, Prolo P, Sutton RL. Injury severity differentially affects short-and long-term neuroendocrine outcomes of traumatic brain injury. Journal of neurotrauma. 2008;25(4):311-23.

    Article  PubMed  Google Scholar 

  74. Sutton RL, Lescaudron L, Stein DG. Unilateral cortical contusion injury in the rat: vascular disruption and temporal development of cortical necrosis. Journal of neurotrauma. 1993;10(2):135-49.

    Article  CAS  PubMed  Google Scholar 

  75. Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, et al. Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. Experimental gerontology. 2008;43(4):339-46.

    Article  CAS  PubMed  Google Scholar 

  76. Kohara Y, Kuwahara R, Kawaguchi S, Jojima T, Yamashita K. Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring. Physiology & behavior. 2014;130:40-6.

    Article  CAS  Google Scholar 

  77. Komaki A, Karimi SA, Salehi I, Sarihi A, Shahidi S, Zarei M. The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats. Pharmacology Biochemistry and Behavior. 2015;131:98-103.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The research was supported in part by grants from Hamadan University of Medical Sciences and Iran University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Razieh Hajisoltani

  2. Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Soraya Mehrabi

  3. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Soraya Mehrabi

  4. Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mona Rahdar

  5. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Seyed Asaad Karimi

  6. Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Seyed Asaad Karimi

Authors
  1. Razieh Hajisoltani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soraya Mehrabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mona Rahdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyed Asaad Karimi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SAK designed the project, wrote the manuscript and performed the statistical analysis, revised the manuscript, and supervised the project. RH, MR, and SM were involved in laboratory works and experimental design of the work. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Seyed Asaad Karimi.

Ethics declarations

Consent for publication

Not applicable.

Ethics approval and consent to participate

All experimental procedures using rats were conducted in accordance with the animal care and use guidelines approved by the institutional ethics committee at Hamadan University of Medical Sciences (ethical approval reference number: IR.UMSHA.REC.1397.954) and were performed in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals.

Competing interests

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hajisoltani, R., Mehrabi, S., Rahdar, M. et al. The effects of Na+-K+-2Cl− cotransporter inhibition on passive avoidance learning and memory deficit in a rat model of traumatic brain injury. Neurosci Behav Physi 52, 806–815 (2022). https://doi.org/10.1007/s11055-022-01281-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-022-01281-9

Keywords

Search

Navigation