title: Chronic cocaine disrupts neurovascular networks and cerebral function: optical imaging studies in rodents.
abstract: Cocaine abuse can lead to cerebral strokes and hemorrhages secondary to cocaine's cerebrovascular effects, which are poorly understood. We assessed cocaine's effects on cerebrovascular anatomy and function in the somatosensory cortex of the rat's brain. Optical coherence tomography was used for in vivo imaging of three-dimensional cerebral blood flow (CBF) networks and to quantify CBF velocities (CBFv), and multiwavelength laser-speckle-imaging was used to simultaneously measure changes in CBFv, oxygenated (Δ[HbO2] ) and deoxygenated hemoglobin (Δ[HbR] ) concentrations prior to and after an acute cocaine challenge in chronically cocaine exposed rats. Immunofluorescence techniques on brain slices were used to quantify microvasculature density and levels of vascular endothelial growth factor (VEGF). After chronic cocaine (2 and 4 weeks), CBFv in small vessels decreased, whereas vasculature density and VEGF levels increased. Acute cocaine further reduced CBFv and decreased Δ[HbO2] and this decline was larger and longer lasting in 4 weeks than 2 weeks cocaine-exposed rats, which indicates that risk for ischemia is heightened during intoxication and that it increases with chronic exposures. These results provide evidence of cocaine-induced angiogenesis in cortex. The CBF reduction after chronic cocaine exposure, despite the increases in vessel density, indicate that angiogenesis was insufficient to compensate for cocaine-induced disruption of cerebrovascular function.
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United StatesbHuazhong University of Science and Technology, Tongji Hospital, Tongji Medical College, Department of Neurology, Wuhan 430030, China.
authors: Qiujia
authors: Q
authors: Zhang
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United States.
authors: Jiang
authors: J
authors: You
authors: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20857, United States.
authors: Nora D
authors: ND
authors: Volkow
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United States.
authors: Jeonghun
authors: J
authors: Choi
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United States.
authors: Wei
authors: W
authors: Yin
authors: Huazhong University of Science and Technology, Tongji Hospital, Tongji Medical College, Department of Neurology, Wuhan 430030, China.
authors: Wei
authors: W
authors: Wang
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United States.
authors: Yingtian
authors: Y
authors: Pan
authors: Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794, United States.
authors: Congwu
authors: C
authors: Du
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000633:toxicity*; D004867:Equipment Design; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000187:drug effects; D010108:Oxyhemoglobins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D041623:Tomography, Optical Coherence / Q000379:methods*; D036401:Toxicity Tests, Chronic
chemical_list: D010108:Oxyhemoglobins; D003042:Cocaine