title: fMRI of delayed albumin treatment during stroke recovery in rats: implication for fast neuronal habituation in recovering brains.
abstract: Accumulating experimental and clinical data suggest that albumin may be neuroprotective for stroke. Here, we use functional magnetic resonance imaging (fMRI) to evaluate the therapeutic efficacy of albumin and its effects on the recovery of stimuli-induced cerebral hemodynamics. For this purpose, fMRI activity in the ipsilesional somatosensory (SS) cortex was assessed using a well established rat model of transient 90 min focal ischemia and electrical forelimb stimulation. Rats were treated with either saline or albumin via intracerebroventricular injections at 12 h post-stroke onset. Despite this delayed treatment time, when compared to the saline-treated rats (n=7), there were significant enhancements of the fMRI activation in the albumin-treated rats (n=6) for both blood oxygenation level dependence (BOLD) and functional cerebral blood volume (fCBV) responses. Interestingly, the temporal characteristics of the ipsilesional SS BOLD responses in the albumin-treated rats appeared considerably altered compared to those of contralesional responses while such temporal alterations were not pronounced for the fCBV responses. These characteristic fMRI temporal profiles of the albumin-treated brains may be due to altered neuronal responses rather than altered integrity of neurovascular coupling, which implies an unusually fast habituation of neuronal responses in the lesional SS cortex. The correlation between various MRI-derived structural parameters and the fMRI response magnitude was also characteristic for albumin and control groups. Taken together, these data suggest that restoration of fMRI response magnitudes, temporal profiles, and correlations with structure may reveal the extent and specific traits of albumin treatment associated stroke recovery.
authors.affiliation: Athinoula Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. spmn@nmr.mgh.harvard.edu
authors.forename: Young R
authors.initials: YR
authors.lastname: Kim
authors.forename: Maurits P A
authors.initials: MP
authors.lastname: van Meer
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Mandeville
authors.forename: Emiri
authors.initials: E
authors.lastname: Tejima
authors.forename: George
authors.initials: G
authors.lastname: Dai
authors.forename: Kamil
authors.initials: K
authors.lastname: Topalkara
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qui
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
mesh_terms: D000418:Albumins / Q000627:therapeutic use*; D000465:Algorithms; D000818:Animals; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000473:pathology; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000418:Albumins; D010100:Oxygen