TY - JOUR
T1 - Rapamycin protects against early brain injury independent of cerebral blood flow changes in a mouse model of subarachnoid haemorrhage
AU - Sasaki, Kazumasu
AU - Yamamoto, Shuzo
AU - Mutoh, Tatsushi
AU - Tsuru, Yoshiharu
AU - Taki, Yasuyuki
AU - Kawashima, Ryuta
N1 - Funding Information:
Japan Society for the Promotion of Science, Grant/Award Number: 17K11563; Cooperative Research Project Program of Joint Usage/Research Center at the IDAC, Tohoku University, Grant/Award Number: H29-1
Funding Information:
We thank Drs. Hirokazu Tsubone and Yasuko Tatewaki for assisting in blinded evaluation of imaging and neurological studies and statistical analyses. This study was supported by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science and Cooperative Research Project Program of Joint Usage/Research Center at the IDAC, Tohoku University.
Publisher Copyright:
© 2018 John Wiley & Sons Australia, Ltd
PY - 2018/8
Y1 - 2018/8
N2 - We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Pretreatment with rapamycin, an mTOR kinase inhibitor, resulted in better recovery from cerebral hypoxia early after SAH than control (P <.05), while the values of peak flow velocity in the middle cerebral artery did not change significantly (P >.05). Average distance travelled and the ratio of central-area distance/total travelled distance determined by open-field test after day 14 was significantly higher in mice pretreated with rapamycin than in control mice (P <.05). Inhibition of the mTOR pathway could be protective against post-SAH early brain injury, ameliorating brain tissue hypoxia and locomotor hypoactivity.
AB - We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Pretreatment with rapamycin, an mTOR kinase inhibitor, resulted in better recovery from cerebral hypoxia early after SAH than control (P <.05), while the values of peak flow velocity in the middle cerebral artery did not change significantly (P >.05). Average distance travelled and the ratio of central-area distance/total travelled distance determined by open-field test after day 14 was significantly higher in mice pretreated with rapamycin than in control mice (P <.05). Inhibition of the mTOR pathway could be protective against post-SAH early brain injury, ameliorating brain tissue hypoxia and locomotor hypoactivity.
KW - cerebral blood flow
KW - early brain injury
KW - mammalian target of rapamycin
KW - mouse model
KW - subarachnoid haemorrhage
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U2 - 10.1111/1440-1681.12950
DO - 10.1111/1440-1681.12950
M3 - Letter
C2 - 29676052
AN - SCOPUS:85050460835
SN - 0305-1870
VL - 45
SP - 859
EP - 862
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 8
ER -