Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.

Appearance of osteoporosis in rat experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by transient paralysis followed by recovery. To evaluate whether transient paralysis in EAE affects bone density, tibiae of EAE rats were morphologically investigated using micro-computed tomography and histology. The parameters of bone health were significantly reduced at the peak stage of EAE rats relative to those of controls (p < 0.05). The reduction of bone density was found to remain unchanged, even in the recovery stage. Collectively, the present data suggest that osteoporosis occurs in paralytic rats with monophasic EAE, possibly through the disuse of hindlimbs and/or autoimmune inflammation.

Protective effect of ethyl acetate extract of Ishige okamurae against carbon tetrachloride-induced acute liver injury in rats / 대한수의학회지

Several compounds and extracts isolated from a brown alga, Ishige (I.) okamurae, exhibit anti-oxidant and anti-inflammatory effects. The present study investigated whether the ethyl acetate (EtOAc) fraction of I. okamurae (EFIO) could ameliorate carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Sprague-Dawley rats were intraperitoneally (i.p.) administered with EFIO at 10 or 50 mg/kg per day for 2 consecutive days before CCl4 injection (3.3 mL/kg, i.p.). Twenty four hours later, the rats were anesthesized with diethyl ether and dissected. Pretreatment with EFIO significantly reduced the increased serum levels of alanine aminotransferase and aspartate aminotransferase in CCl4-treated rats. Pretreatment with EFIO also significantly inhibited the reduced activities of superoxide dismutase and catalase in the CCl4-injured liver. Histopathological evaluations showed that hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration induced by CCl4 treatment were ameliorated by the administration of EFIO. Additionally, liver immunohistochemical analyses revealed the marked reduction in ED1-positive monocyte-like macrophages in EFIO-pretreated rats given CCl4. These results suggest that EFIO ameliorates CCl4-induced liver injury, possibly through the inhibition of oxidative stress.