Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/ijms22158276
Keywords
3,6 '-dithiopomalidomide; pomalidomide; traumatic brain injury; neurodegeneration; cognitive deficits; neuroinflammation; microgliosis; astrogliosis; immunomodulatory imide drugs
Funding
- Ministry of Science and Technology, Taiwan [MOST 110-2314-B-038-106, MOST 108-2321-B-038-008]
- Sunny Brain Tumor and Brain Disease Research and Development Fund, Taipei Medical University, Taipei, Taiwan
- Intramural Research Program, National Institute on Aging, National Institutes of Health, USA
- National Institutes of Health, USA [R56 AG057028]
- Technology Development Program of MSS [S2782046]
- National Research Foundation (NRF) - Korean Government [2021M3A9G2015889]
- National Research Foundation of Korea [2021M3A9G2015889] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Pomalidomide analog and 3,6'-dithioPom show protective effects on hippocampal neurodegeneration, microgliosis, and behavioral impairments induced by TBI, while attenuating neuroinflammation caused by TBI.
Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6 '-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.
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