Abstract
Background
Hypoxia–ischemia (HI) is a major cause of neurological damage in preterm newborn. Swimming during pregnancy alters the offspring’s brain development. We tested the effects of swimming during pregnancy in the very immature rat brain.
Methods
Female Wistar rats (n=12) were assigned to the sedentary (SE, n=6) or the swimming (SW, n=6) group. From gestational day 0 (GD0) to GD21 the rats in the SW group were made to swim for 20 min/day. HI on postnatal day (PND) 3 rats caused sensorimotor and cognitive impairments. Animals were distributed into SE sham (SESH), sedentary HIP3 (SEHI), swimming sham (SWSH), and swimming HIP3 (SWHI) groups. At PND4 and PND5, Na+/K+-ATPase activity and brain-derived neurotrophic factor (BDNF) levels were assessed. During lactation and adulthood, neurological reflexes, sensorimotor, anxiety-related, and cognitive evaluations were made, followed by histological assessment at PND60.
Results
At early stages, swimming caused an increase in hippocampal BDNF levels and in the maintenance of Na+/K+-ATPase function in the SWHI group. The SWHI group showed smaller lesions and the preservation of white matter tracts. SEHI animals showed a delay in reflex maturation, which was reverted in the SWHI group. HIP3 induced spatial memory deficits and hypomyelination in SEHI rats, which was reverted in the SWHI group.
Conclusion
Swimming during pregnancy neuroprotected the brains against HI in very immature neonatal rats.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Volpe JJ . The encephalopathy of prematurity-brain injury and impaired brain development inextricably intertwined. Semin Pediatr Neurol 2009;16:167–78.
Johnson S . Cognitive and behavioural outcomes following very preterm birth. Semin Fetal Neonatal Med 2007;12:363–73.
Khwaja O, Volpe JJ . Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child 2008;93:F153–61.
Silbereis JC, Huang EJ, Back SA, Rowitch DH . Towards improved animal models of neonatal white matter injury associated with cerebral palsy. Dis Model Mech 2010;3:678–88.
Fatemi A, Wilson MA, Johnston M V . Hypoxic-ischemic encephalopathy in the term infant. Clin Perinatol 2009;36:835–52.
Grisar T . Glial and neuronal Na+-K+ pump in epilepsy. Ann Neurol 1984;Suppl:S128-34:16.
Yu SP . Na+, K+-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death. Biochem Pharmacol 2003;66:1601–9.
Wyse A, Streck EL, Worm P, Wajner A, Ritter F, Netto CA . Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem Res 2000;25:971–5.
Sanches EF, Arteni NS, Nicola F, Boisserand L, Willborn S, Netto CA . Early hypoxia-ischemia causes hemisphere and sex-dependent cognitive impairment and histological damage. Neuroscience 2013;237:208–15.
Sizonenko S V, Sirimanne E, Mayall Y, Gluckman PD, Inder T, Williams C . Selective cortical alteration after hypoxic-ischemic injury in the very immature rat brain. Pediatr Res 2003;54:263–9.
Cengiz P, Uluc K, Kendigelen P et al, Chronic neurological deficits in mice after perinatal hypoxia and ischemia correlate with hemispheric tissue loss and white matter injury detected by MRI. Dev Neurosci 2011;33:270–9.
Huang Z, Liu J, Cheung PY, Chen C . Long-term cognitive impairment and myelination deficiency in a rat model of perinatal hypoxic-ischemic brain injury. Brain Res 2009;1301:100–9.
Tai W, Burke KA, Dominguez JF, Gundamraj L, Turman JE . Growth deficits in a postnatal day 3 rat model of hypoxic-ischemic brain injury. Behav Brain Res 2009;202:40–9.
Bale TL . Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 2015;16:1–13.
Heart S, Katz VL . Exercise in water during pregnancy. Clin Obstet Gynecol 2003;46:432–41.
Lee HH, Kim H, Lee JW et al, Maternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups. Brain Dev 2006;28:147–54.
Akhavan MM, Foroutan T, Safari M, Sadighi-Moghaddam B, Emami-Abarghoie M, Rashidy-Pour A . Prenatal exposure to maternal voluntary exercise during pregnancy provides protection against mild chronic postnatal hypoxia in rat offspring. Pak J Pharm Sci 2012;25:233–8.
Marcelino TB, Longoni A, Kudo KY et al, Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats. Neuroscience 2013;246:28–39.
Parnpiansil P, Jutapakdeegul N, Chentanez T, Kotchabhakdi N . Exercise during pregnancy increases hippocampal brain-derived neurotrophic factor mRNA expression and spatial learning in neonatal rat pup. Neurosci Lett 2003;352:45–8.
Akhavan MM, Emami-Abarghoie M, Safari M et al, Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups. Neuroscience 2008;151:1173–83.
Kim DH, Zhao X . BDNF protects neurons following injury by modulation of caspase activity. Neurocrit Care 2005;3:71–6.
Han BH, Holtzman DM . BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J Neurosci 2000;20:5775–81.
Sanches EF, Arteni NS, Scherer EB et al, Are the consequences of neonatal hypoxia-ischemia dependent on animals’ sex and brain lateralization? Brain Res 2013;1507:105–114.
Smith AL, Alexander M, Rosenkrantz TS, Sadek ML, Fitch RH . Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp Neurol 2014;254:54–67.
Lubics A, Reglodi D, Tamás A et al, Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury. Behav Brain Res 2005;157:157–65.
Ten VS, Bradley-Moore M, Gingrich JA, Stark RI, Pinsky DJ . Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy. Behav Brain Res 2003;145:209–19.
Barth TM, Stanfield BB . The recovery of forelimb-placing behavior in rats with neonatal unilateral cortical damage involves the remaining hemisphere. J Neurosci 1990;10:3449–59.
Sizonenko S V, Kiss JZ, Inder T, Gluckman PD, Williams CE . Distinctive neuropathologic alterations in the deep layers of the parietal cortex after moderate ischemic-hypoxic injury in the P3 immature rat brain. Pediatr Res 2005;57:865–72.
Sanches EF, Arteni N, Nicola F, Aristimunha D, Netto C . a. Sexual dimorphism and brain lateralization impact behavioral and histological outcomes following hypoxia–ischemia in P3 and P7 rats. Neuroscience 2015;290:581–93.
Raymond M . Chronic perinatal hypoxia reduces GLAST function in astrocytes through the JAK/STAT pathway. J Neurosci Res 2012;31:17864–71.
Lees GJ, Lehmann A, Sandberg M, Hamberger A . The neurotoxicity of ouabain, a sodium-potassium ATPase inhibitor, in the rat hippocampus. Neurosci Lett 1990;120:159–62.
Veldhuis WB, van der Stelt M, Delmas F et al, In vivo excitotoxicity induced by ouabain, a Na+/K+-ATPase inhibitor. J Cereb Blood Flow Metab 2003;23:62–74.
Leite HR, Mourão FAG, Drumond LE et al, Swim training attenuates oxidative damage and promotes neuroprotection in cerebral cortical slices submitted to oxygen glucose deprivation. J Neurochem 2012;123:317–24.
Tian D, Dmitrieva RI, Doris PA et al, Protein kinase M zeta regulation of Na/K ATPase: a persistent neuroprotective mechanism of ischemic preconditioning in hippocampal slice cultures. Brain Res 2008;1213:127–39.
Oselkin M, Tian D, Bergold PJ . Low-dose cardiotonic steroids increase sodium-potassium ATPase activity that protects hippocampal slice cultures from experimental ischemia. Neurosci Lett 2010;473:67–71.
Gomes Da Silva S, De Almeida AA, Fernandes J et al, Maternal exercise during pregnancy increases BDNF levels and cell numbers in the hippocampal formation but not in the cerebral cortex of adult rat offspring. PLoS ONE 2016;11:1–15.
Chavez-Valdez R, Martin LJ, Razdan S, Gauda EB, Northington FJ . Sexual dimorphism in BDNF signaling after neonatal hypoxia-ischemia and treatment with necrostatin-1. Neuroscience 2014;260:106–19.
Wang Y, Cao M, Liu A et al, Changes of inflammatory cytokines and neurotrophins emphasized their roles in hypoxic-ischemic brain damage. Int J Neurosci 2013;123:191–5.
Marcelino TB, de Lemos Rodrigues PI, Miguel PM, Netto CA, Pereira Silva LO, Matté C . Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia. Brain Res 2015;1622:91–101.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
The first two authors contributed equally to this work.
Statement of Financial Support
We are thankful to the following Brazilian agencies for their financial support: CNPq, CAPES, and FAPERGS.
Disclaimer
No writing assistance was utilized in the preparation of the manuscript.
Rights and permissions
About this article
Cite this article
Sanches, E., Durán-Carabali, L., Tosta, A. et al. Pregnancy swimming causes short- and long-term neuroprotection against hypoxia–ischemia in very immature rats. Pediatr Res 82, 544–553 (2017). https://doi.org/10.1038/pr.2017.110
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2017.110
