Pharmacological fMRI

Region-specific functional recovery of the mouse brain following transient focal ischemia using fMRI.

The structural integrity of brain tissue during the acute phase following ischemic stroke does not necessarily imply recovery of function. The information on region-specific relationship between structural and functional integrities after stroke is limited in general.

Functional magnetic resonance imaging using pharmacological stimulation paradigms that induce a global brain response is a sensitive method for studying functional changes in the rodent brain in vivo. The systemic infusion of the GABA(A) antagonist bicuculline induces the increase of spontaneous firing rate in neurons due to disinhibition of the GABA(A)–mediated currents. The neuronal activation is accompanied by the increase in regional Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV).

Differential CBV response to bicuculline stimulation is observed in the rat brain following transient ischemia. We extend this method to identify regions of impaired functionality in post-ischemic mouse brain.

Using magnetite nanoparticles as an intravascular contrast agent, we measure changes in local CBV, induced by the systemic infusion of bicuculline in ischemic mice following 30 minutes of intraluminal middle cerebral artery (MCA) occlusion. T2-, diffusion weighted (DW) images, and fMRI were acquired at 24 hr, 72 hr and 7 days of reperfusion period. Changes in CBV are analyzed in striatal, cortical and subcortical regions.

Methods

• MR: 7T scanner, ph-MRI
• Paradigm: bicuculine stimulation
• Subjects: NMRI-Han male mice

Temporal evolution of CBV changes following stimulation with bicuculline in control mice.

Collaborations

Dr. Martin Rausch, In-vivo Imaging DT, Novartis Institutes for Bio-medical Research, Discovery Technologies/Analytical and Imaging Sciences, Basel, Switzerland

Support

NCCR on Neural Plasticity and Repair

Contact

Prof. Dr. Ernst Martin
ernst.martinkispi.uzh.ch

Former Collaborators

Dr. Thomas Loenneker