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. 2017 Apr;12(4):596-602.
doi: 10.4103/1673-5374.205099.

Aerobic exercise combined with huwentoxin-I mitigates chronic cerebral ischemia injury

Hai-Feng Mao  1   2 , Jun Xie  2 , Jia-Qin Chen  1 , Chang-Fa Tang  1 , Wei Chen  1 , Bo-Cun Zhou  1 , Rui Chen  1 , Hong-Lin Qu  1   2 , Chu-Zu Wu  2
Affiliations

Aerobic exercise combined with huwentoxin-I mitigates chronic cerebral ischemia injury

Hai-Feng Mao et al. Neural Regen Res. 2017 Apr.

Abstract

Ca2+ channel blockers have been shown to protect neurons from ischemia, and aerobic exercise has significant protective effects on a variety of chronic diseases. The present study injected huwentoxin-I (HWTX-I), a spider peptide toxin that blocks Ca2+ channels, into the caudal vein of a chronic cerebral ischemia mouse model, once every 2 days, for a total of 15 injections. During this time, a subgroup of mice was subjected to treadmill exercise for 5 weeks. Results showed amelioration of cortical injury and improved neurological function in mice with chronic cerebral ischemia in the HWTX-I + aerobic exercise group. The combined effects of HWTX-I and exercise were superior to HWTX-I or aerobic exercise alone. HWTX-I effectively activated the Notch signal transduction pathway in brain tissue. Aerobic exercise up-regulated synaptophysin mRNA expression. These results demonstrated that aerobic exercise, in combination with HWTX-I, effectively relieved neuronal injury induced by chronic cerebral ischemia via the Notch signaling pathway and promoting synaptic regeneration.

Keywords: Notch signaling pathway; aerobic exercise; calcium overload; chronic cerebral ischemia; huwentoxin-I; nerve regeneration; neural regeneration.

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Conflict of interest statement

Conflicts of interest: None declared.

Figures

Figure 1
Figure 1
Establishment of chronic cerebral ischemia models. (A, B) Isolating the right common carotid artery. (C) Ligating the right common carotid artery.
Figure 2
Figure 2
Aerobic exercise. The mice were subjected to running on a treadmill.
Figure 3
Figure 3
Effects of aerobic exercise and HWTX-I on neurological function in mice with chronic cerebral ischemia. Neurological function was assessed using a 28-point neurological deficit score (Clark Neurological function score). A higher score represents more severe neurological deficits. (A) Immediately after group assignment; (B) the fifth weekend. Data are expressed as mean ± SD (n = 10 per group). **P < 0.01, vs. model group; #P < 0.05, vs. HWTX-I group (one-way analysis of variance). HWTX-I: Huwentoxin-I.
Figure 4
Figure 4
Effects of aerobic exercise and HWTX-I on morphological changes in the cerebral cortex of chronic cerebral ischemia mice (Nissl staining, × 200). (A) Model group; (B) HWTX-I group; (C) aerobic exercise group; (D) HWTX-I + aerobic exercise group. Red arrows show vacuoles; yellow arrows show pyknosis; white arrow shows nucleolus; orange arrow shows Nissl body at the periphery. Scale bars: 100 μm. HWTX-I: Huwentoxin-I.
Figure 5
Figure 5
Effects of aerobic exercise and HWTX-I on Notch1, Jagged1, NCX1, SYP, and CaBP-D28k mRNA expressions in the brain (A) and blood (B) of chronic cerebral ischemia mice (real-time polymerase chain reaction). Data are expressed as the mean ± SD (n = 10 per group). *P < 0.05, **P < 0.01, vs. model group (one-way analysis of variance). HWTX-I: Huwentoxin-I.
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