Large molecular weight blood protein, Fibrinogen (Fg) is an inflammatory marker and inducer of inflammation. It is shown that 9 days after cortical contusion injury (CCI) resulting in mild to moderate traumatic brain injury (TBI), brain microvessels are no longer raptured. However, we found that 14 days after CCI in mice, Fg extravasates via mainly caveolar transcytosis and deposited in vasculo-astrocyte interface. These newly discovered phenomena were associated with short-term memory reduction. We are currently studying effects of Fg-activated astrocytes and Fg and cellular prion protein complex formation on neurodegeneration and the resultant loss of neuronal function during mild to moderate TBI, and pursue novel strategies to identify targets for potential therapeutic interventions in newly discovered mechanisms involved in STM reduction during neuroinflammatory diseases.

1. Charkviani M, Muradashvili N, Sulimai N, Lominadze D. Fibrinogen-cellular prion protein complex formation on astrocytes. Journal of Neurophysiology. 2020; 124(2): 536-543. doi: 10.1152/jn.00224.2020.

2. Clark VD, Layson A, Charkviani M, Muradashvili N, Lominadze D. Hyperfibrinogenemia-mediated astrocyte activation. Brain Research. 2018; 1699: 158-165.

3. Muradashvili N, Tyagi SC, Lominadze D. Localization of fibrinogen in the vasculo-astrocyte interface after cortical contusion injury in mice. Brain Sciences, 2017; 7(7): pii: E77, doi: 10.3390/brainsci7070077. PMCID: PMC5532590

4. Muradashvili N, Tyagi R, Tyagi N, Tyagi SC, Lominadze D. Cerebrovascular disorders caused by hyperfibrinogenemia. Journal of Physiology. 2016; 594(20): 5941-5957. PMCID: PMC5063932.

5. Muradashvili N, Benton RL, Saatman K, Tyagi SC, Lominadze D. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice. Special issue entitled: “Mechanisms and therapies for acute CNS insults”. (Ed. Raghu Vemuganti). Metabolic Brain Disease. 2015; 30(2): 411-426. PMCID: PMC4213324

6. Muradashvili N, Khundmiri SJ, Tyagi R, Gartung A, Dean WL, Lee M-J, Lominadze D. Sphingolipids affect fibrinogen-induced caveolar transcytosis and cerebrovascular permeability. Am. J. Physiol. Cell Physiol. 2014; 307(2): C169-C179. PMCID: PMC4101621

7. Muradashvili N, Tyagi R, Lominadze D. A dual-tracer method for differentiating transendothelial transport from paracellular leakage in vivo and in vitro. Frontiers in Physiology, Vascular Physiology. 2012; 3: Article 166. doi: 10.3389/fphys.2012.00166 Featured in “Antibody Resource” PMCID: PMC3385581

8. Muradashvili N, Qipshidze N, Munjal C, Givvimani S. Benton R, Tyagi, SC, Lominadze D. Fibrinogen-induced increased pial venular permeability in mice. J Cerebral Blood Flow and Metabolism. 2012; 32(1): 150-163. Cover photo. PMCID: PMC3256415

9. Lominadze D, Dean WL. Involvement of fibrinogen specific binding in erythrocyte aggregation. FEBS Letters. 2002; 517(1-3): 41-44. (Equal contribution by the authors)