Perivascular and perineural extension of formed and soluble blood elements in an intracerebral hemorrhage rat model

The perivascular and perineural extension of hematoma has recently been observed in the brain after intracerebral hemorrhage (ICH), which is formed by the leakage of hematoma via the Virchow–Robin spaces (VRS) and the spaces around the nerve fibers (perineurium). The present study investigated the perivascular and perineural extension of a hematoma by studying the distribution of the formed and soluble blood elements labeled with different fluorescein dyes at different times after ICH in a rat model. The ICH rat model was prepared using a modified double injection method. Autologous blood, which contained fluorescein isothiocyanate (FITC)-labeled RBCs or carboxytetramethylrhodamine (TAMRA)-labeled BSA, was injected into the center of the left caudate nucleus. Brain sections were prepared and observed by overlaying fluorescence and hematoxylin and eosin stained images. The formed blood elements extended mainly into the VRS and perineurium in the perihematomal tissue and ipsilateral brain regions near the hematoma. The soluble blood elements extended more extensively to almost all regions of the brain, including some remote brain areas, such as the contralateral cerebral hemisphere and brainstem. Moreover, the fluorescein dyes were observed in lymph sinuses in the bilateral deep cervical lymph nodes as early as 1 hour after ICH. Lymphostasis, which peaked three days after ICH, was observed in the brain tissues around hematoma. The current findings suggest that the perivascular and perineural extension of hematomas widespread distributes in the central nervous system, and is involved in a series of pathologic processes in ICH, such as the remote effects of a hematoma and lymphatic encephalopathy.