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Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats

View Article: PubMed Central - PubMed

ABSTRACT

Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH) is closely related to the progression of brain damage, little is known about the molecular mechanism underlying its development. High mobility group box-1 (HMGB1) plays an important role as an initial inflammatory mediator in SAH. In this study, an SAH rat model was employed to evaluate the effects of anti-HMGB1 monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb administration significantly suppressed these effects. Up-regulations of inflammation-related molecules and vasoconstriction-mediating receptors in the BA of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated the enhanced vasocontractile response to thrombin of the isolated BA from SAH rats and prevented activation of cerebrocortical microglia. Moreover, locomotor activity and weight loss recovery were also enhanced by anti-HMGB1 mAb administration. The vasocontractile response of the BA under SAH may be induced by events that are downstream of responses to HMGB1-induced inflammation and inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel therapeutic strategy for DCV and early brain injury after SAH.

No MeSH data available.


Related in: MedlinePlus

Effect of anti-HMGB1 mAb on neurological symptoms and body weight after SAH.An open field test was performed at 48 hr after the SAH in rats administered anti-HMGB1 mAb or control IgG at both 5 min and 24 hr after blood injection. The total distance moved (a) and moving velocity (b) were measured to assess locomotor activity. (c) Changes in the body weights of rats were also measured once daily over the 7 days after the SAH procedure. Results are shown for the sham group (Sham, n = 4), the control IgG-treated group (Cont IgG, n = 6), and the anti-HMGB1 mAb-treated group (α-HMGB1, n = 6). Values represent the means ± SE. *P < 0.05, **P < 0.01 compared with the sham group. ##P < 0.01 compared with the control IgG-treated group. N.S.: Not significant.
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f6: Effect of anti-HMGB1 mAb on neurological symptoms and body weight after SAH.An open field test was performed at 48 hr after the SAH in rats administered anti-HMGB1 mAb or control IgG at both 5 min and 24 hr after blood injection. The total distance moved (a) and moving velocity (b) were measured to assess locomotor activity. (c) Changes in the body weights of rats were also measured once daily over the 7 days after the SAH procedure. Results are shown for the sham group (Sham, n = 4), the control IgG-treated group (Cont IgG, n = 6), and the anti-HMGB1 mAb-treated group (α-HMGB1, n = 6). Values represent the means ± SE. *P < 0.05, **P < 0.01 compared with the sham group. ##P < 0.01 compared with the control IgG-treated group. N.S.: Not significant.

Mentions: Impairments of coordinated locomotor activity after SAH were assessed by using an open field test in which the rats were exposed to a new environment. Both the total distance moved over 5 min and the average moving velocity were lower in the control IgG-treated group than in the sham group. The lower locomotor activities in SAH control rats were restored to healthy levels by the administration of anti-HMGB1 mAb (Fig. 6a,b).


Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats
Effect of anti-HMGB1 mAb on neurological symptoms and body weight after SAH.An open field test was performed at 48 hr after the SAH in rats administered anti-HMGB1 mAb or control IgG at both 5 min and 24 hr after blood injection. The total distance moved (a) and moving velocity (b) were measured to assess locomotor activity. (c) Changes in the body weights of rats were also measured once daily over the 7 days after the SAH procedure. Results are shown for the sham group (Sham, n = 4), the control IgG-treated group (Cont IgG, n = 6), and the anti-HMGB1 mAb-treated group (α-HMGB1, n = 6). Values represent the means ± SE. *P < 0.05, **P < 0.01 compared with the sham group. ##P < 0.01 compared with the control IgG-treated group. N.S.: Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121891&req=5

f6: Effect of anti-HMGB1 mAb on neurological symptoms and body weight after SAH.An open field test was performed at 48 hr after the SAH in rats administered anti-HMGB1 mAb or control IgG at both 5 min and 24 hr after blood injection. The total distance moved (a) and moving velocity (b) were measured to assess locomotor activity. (c) Changes in the body weights of rats were also measured once daily over the 7 days after the SAH procedure. Results are shown for the sham group (Sham, n = 4), the control IgG-treated group (Cont IgG, n = 6), and the anti-HMGB1 mAb-treated group (α-HMGB1, n = 6). Values represent the means ± SE. *P < 0.05, **P < 0.01 compared with the sham group. ##P < 0.01 compared with the control IgG-treated group. N.S.: Not significant.
Mentions: Impairments of coordinated locomotor activity after SAH were assessed by using an open field test in which the rats were exposed to a new environment. Both the total distance moved over 5 min and the average moving velocity were lower in the control IgG-treated group than in the sham group. The lower locomotor activities in SAH control rats were restored to healthy levels by the administration of anti-HMGB1 mAb (Fig. 6a,b).

View Article: PubMed Central - PubMed

ABSTRACT

Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH) is closely related to the progression of brain damage, little is known about the molecular mechanism underlying its development. High mobility group box-1 (HMGB1) plays an important role as an initial inflammatory mediator in SAH. In this study, an SAH rat model was employed to evaluate the effects of anti-HMGB1 monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb administration significantly suppressed these effects. Up-regulations of inflammation-related molecules and vasoconstriction-mediating receptors in the BA of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated the enhanced vasocontractile response to thrombin of the isolated BA from SAH rats and prevented activation of cerebrocortical microglia. Moreover, locomotor activity and weight loss recovery were also enhanced by anti-HMGB1 mAb administration. The vasocontractile response of the BA under SAH may be induced by events that are downstream of responses to HMGB1-induced inflammation and inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel therapeutic strategy for DCV and early brain injury after SAH.

No MeSH data available.


Related in: MedlinePlus