Ahmadian Mehdi, Erskine Erin, Wainman Liisa, Wearing Oliver H, Duffy Jennifer S, Stewart Liam C, Hoiland Ryan L, Taki Alissa, Perim Raphael R, Mitchell Gordon S, Little Jonathan P, Mueller Patrick J, Foster Glen E, West Christopher R
School of Kinesiology, Faculty of Education, University of British Columbia, Vancouver, BC, Canada; International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada; Centre for Chronic Disease Prevention and Management, University of British Columbia, Kelowna, BC, Canada; Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada; Centre for Chronic Disease Prevention and Management, University of British Columbia, Kelowna, BC, Canada; Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Exp Neurol. 2025 Feb;384:115054. doi: 10.1016/j.expneurol.2024.115054. Epub 2024 Nov 14.
The loss of medullary control of spinal circuits controlling the heart and blood vessels is a unifying mechanism linking both hemodynamic instability and the risk for cardiovascular diseases (CVD) following spinal cord injury (SCI). As such, new avenues to regulate sympathetic activity are essential to mitigate CVD in this population. Acute intermittent hypoxia (AIH) induces a type of neuroplasticity known as long-term facilitation (LTF), a persistent increase in nerve activity post-AIH in spinal motor circuits. Whether LTF occurs within the sympathetic circuit following SCI is largely unknown. We aimed to test whether AIH elicits sympathetic LTF (i.e., sLTF) and attenuates hypoactivity in sub-lesional splanchnic sympathetic circuits in a male rat model of SCI. In 3 experimental series, we tested whether 1) high-thoracic contusion SCI induces hypoactivity in splanchnic sympathetic nerve activity, 2) AIH elicits sLTF following SCI, and 3) sLTF requires carotid chemoreflex activation or spinal cord tissue hypoxia. Our results indicate that a single-session of AIH therapy (10 × 1 min of FO = 0.1, interspersed with 2 min of FO = 1.0) delivered at 2 weeks following SCI attenuates SCI-induced sympathetic hypoactivity by eliciting sLTF 90 min post-treatment that is independent of peripheral chemoreflex activation and/or spinal cord hypoxia. These findings advance our mechanistic understanding of AIH in the field and yield new insights into factors underpinning AIH-induced sLTF following SCI in a rat model. Our findings also set the stage for the chronic application of AIH to alleviate secondary complications resulting from sympathetic hypoactivity following SCI.
脊髓损伤（SCI）后，脊髓对控制心脏和血管的神经回路的髓质控制丧失，是导致血流动力学不稳定和心血管疾病（CVD）风险的一个共同机制。因此，调节交感神经活动的新途径对于减轻该人群的心血管疾病至关重要。急性间歇性缺氧（AIH）可诱导一种称为长期易化（LTF）的神经可塑性，即AIH后脊髓运动神经回路中神经活动的持续增加。SCI后交感神经回路中是否发生LTF在很大程度上尚不清楚。我们旨在测试AIH是否能引发交感神经LTF（即sLTF），并减轻SCI雄性大鼠模型中损伤平面以下内脏交感神经回路的活动减退。在3个实验系列中，我们测试了：1）高胸段挫伤性SCI是否会导致内脏交感神经活动减退；2）AIH是否能在SCI后引发sLTF；3）sLTF是否需要颈动脉化学反射激活或脊髓组织缺氧。我们的结果表明，在SCI后2周进行单次AIH治疗（10×1分钟的FO = 0.1，穿插2分钟的FO = 1.0），通过在治疗后90分钟引发sLTF来减轻SCI诱导的交感神经活动减退，且该sLTF独立于外周化学反射激活和/或脊髓缺氧。这些发现推进了我们对该领域AIH机制的理解，并为大鼠模型中SCI后AIH诱导sLTF的潜在因素提供了新见解。我们的发现还为长期应用AIH以减轻SCI后交感神经活动减退引起的继发性并发症奠定了基础。
