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Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage

  • Experimental Research - Vascular
  • Published:
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Abstract

Background

It is believed that increased intracranial pressure immediately after subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in worsening clinical status. Arterial flow to the cerebral surfaces is clinically well maintained during clipping surgery regardless of the severity of the World Federation of Neurological Societies grade after SAH. To explore what kinds of changes occur in the cortical microcirculation, not at the cerebral surface, we examined cortical microcirculation after SAH using two-photon laser scanning microscopy (TPLSM).

Methods

SAH was induced in mice with an endovascular perforation model. Following continuous injection of rhodamine 6G, velocities of labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were measured in the cortical capillaries 60 min after SAH with a line-scan method using TPLSM, and the data were compared to a sham group and P-selectin monoclonal antibody-treated group.

Results

Velocities of leukocytes, platelets, and RBCs in capillaries decreased significantly 60 min after SAH. Rolling and adherent leukocytes suddenly prevented other blood cells from flowing in the capillaries. Flowing blood cells also decreased significantly in each capillary after SAH. This no-reflow phenomenon induced by plugging leukocytes was often observed in the SAH group but not in the sham group. The decreased velocities of blood cells were reversed by pretreatment with the monoclonal antibody of P-selection, an adhesion molecule expressed on the surfaces of both endothelial cells and platelets.

Conclusions

SAH caused sudden worsening of cortical microcirculation at the onset. Leukocyte plugging in capillaries is one of the reasons why cortical microcirculation is aggravated after SAH.

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanumacho Omiya-ku, Saitama-city, Saitama, 330-8503, Japan

    Mami Ishikawa, Gen Kusaka & Yuichi Tanaka

  2. Department of Biochemistry School of Medicine, Keio University, Tokyo, Japan

    Mami Ishikawa, Mayumi Kajimura, Takayuki Morikawa, Toshiyuki Tsuji & Makoto Suematsu

  3. Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

    Takayuki Morikawa

  4. Graduate School of Science and Technology, Keio University, Kanagawa, Japan

    Kosuke Tsukada

Authors
  1. Mami Ishikawa
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  2. Mayumi Kajimura
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  3. Takayuki Morikawa
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Corresponding author

Correspondence to Mami Ishikawa.

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Funding

The Japan Society for the Promotion of Science Grant-in-Aid provided financial support in the forms of Scientific Research (22591597, 25462233) funding for M.I. and Scientific Research (21500353, 24500448) funding for M.K. The Japan Science and Technology Agency provided financial support in the form of Exploratory Research for Advanced Technology funding for M.S.

Conflict of interest

None.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Keio University Animal Care and Use Committee (12070–2).

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Comments

The authors provided a very elegant study on the pathophysiology of the cortical microcirculation after subarachnoid hemorrhage (SAH) in a rodent model. They very clearly demonstrated that when a sudden increase of intracranial pressure (ICP) begins after SAH, blood cell velocities in the capillaries decrease significantly and “rolling” and adherent leukocytes plug capillaries, preventing other blood cells from flowing. According to the results here provided, this is the consequence of an ICP rise that determine the compression of capillaries and decrease of blood flow. This in turn causes cerebral ischemic damage and an inflammatory response. This study provides robust evidence about the subsistence of this pathophysiological event and interesting illustrations. Further studies to demonstrate the translational potential of these findings are warranted. In particular, it is true that an abrupt ICP rise is present after SAH. Nevertheless, this cortical dysfunction might be present only in severe SAH cases. I wonder whether it is the persistently elevated ICP, present in severe SAH grades, instead of an abrupt rise with a quick fall that plays a major role. An indication of the intensity and the duration of the ICP rise able to induce such microvessel paralysis would be desirable. Thus, the authors are invited to continue their studies and provide further data on this interesting issue.

Alfredo Conti

Messina, Italy

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Ishikawa, M., Kajimura, M., Morikawa, T. et al. Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage. Acta Neurochir 158, 1057–1067 (2016). https://doi.org/10.1007/s00701-016-2792-6

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  • DOI: https://doi.org/10.1007/s00701-016-2792-6

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