Pathology of the Spinal Cord of C57BL/6J Mice Infected with Rabies Virus (CVS-11 Strain)

Abstract

ABSTRACT. Fixed rabies viruses (CVS-11 strain) were inoculated intramuscularly to C57BL/6J mice, and the pathomorphological changes of the spinal cord including dorsal root spinal ganglion cells were investigated. At 4 days postinoculation (PI), viral antigens were first detected in the spinal neurons and dorsal root spinal ganglion cells without producing morphological changes. At 5 days PI, mild infiltration of lymphocytes was observed around the central canal, small blood vessels and leptomeninges. Cells positive to anti-Iba1 and anti-GFAP antibodies increased significantly from 3 to 5 days PI, respectively. Microglia changed their morphological forms to be ramified or amoeboid, and astroglia extended their cytoplasm from the leptomeninges to the parenchyma. At 7 days PI, apoptotic cells were found in the spinal cord and dorsal root spinal ganglion using TUNEL. We confirmed that most of T lymphocytes and a minority of microglial cells underwent apoptosis, using a combination of TUNEL and immunostaining with antibodies to viral phosphoprotein, CD3, Iba1 and GFAP. On the other hand, astroglial cells and virus-infected nerve cells were negative against TUNEL and cleaved caspase-3 antibody. These findings indicate that T lymphocytes and microglial cells died by apoptosis, whereas virus-infected nerve cells died by necrosis. This was accompanied by increased numbers and morphological changes of glial cells associated with the pathogenesis of CVS-11 in the C57BL/6J mouse.

Role of nitric oxide in the regulation of immune responses during rabies virus infection in mice

“…CVS strain of fixed RABV in suckling, neonatal and adult mice produces encephalitis with marked neuronal apoptosis in various regions of brain when inoculated intracerebrally [15,16]. In contrast, peripheral routes of inoculation of CVS in adult mice showed severe and fatal encephalitis without prominent neuronal apoptosis [3,13,[17][18][19].…”

“…However, in rabies the T cell response was found inefficient being inactivated by the virus [2,12]. Further, cells undergoing death were leukocytes and not neurons, which were confirmed by immunohistochemical studies [2,3,[12][13][14]. The CVS strain of RABV by intracerebral route in mice produces encephalitis with marked neuronal apoptosis [15,16], whereas peripheral routes of inoculation produces severe and fatal encephalitis without prominent neuronal apoptosis [3,13,[17][18][19].…”

“…Rabies virus (RABV), the causative agent of rabies, is a member of the genus Lyssavirus and family Rhabdoviridae [1][2][3]. It is a major zoonotic disease of worldwide occurrence and only few countries are free of rabies that includes the islands like Australia, New Zealand and Scandinavian countries [1,2].…”

Lesions of the Central Nervous System Induced by Intracerebral Inoculation of BALB/c Mice with Rabies Virus (CVS-11)

“…Immunohistochemistry: For detection of rabies virus antigens in tissues, all sections were stained using the streptavidin-biotin-peroxidase complex method using anti-rabbit phosphoprotein (P) [15]. For detection of cell type, the following primary antibodies were used: anti-glial fibrillary acidic protein (GFAP) for astroglial cells (Nichirei Biosciences, Tokyo, Japan); anti-ionized calcium binding adaptor molecule 1 (Iba1) for microglial cells (Wako, Osaka, Japan); anti-CD3 for T lymphocytes (DAKO, Kyoto, Japan); and anti-CD20 for B lymphocytes (Spring Bioscience, Fremont, CA, U.S.A.).…”

“…Previously, we demonstrated that C57BL/6J mice inoculated intramuscularly with CVS-11 showed paralysis with severe spinal lesions [15]. The spinal lesions were composed of the infiltration of T lymphocytes, the increase of microglial cells and astroglial cells and the majority of T lymphocytes exhibited apoptosis.…”