Anti-neuroinflammation effect of zonisamide in early Parkinson’s disease: A chronological PET study
Takashi Matsudaira1, Tatsuhiro Terada1, Tomoyasu Bunai1, Takanori Hashizume2, Masamichi Yokokura3, Hirotsugu Takashima1, Takashi Konishi4, Tomokazu Obi5, Yasuomi Ouchi1
1Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, 2Osaka Ohtani University, 3Psychiatry, Hamamatsu University School of Medicine, 4Neurology, Japanese Red Cross Shizuoka Hospital, 5Neurology, NHO Shizuoka Institute of Epilepsy and Neurological disorders
Objective:
To evaluate the in vivo neuroprotective effect of zonisamide, we examined the chronological change in the microglial activation and nigrostriatal degeneration in the early stage of PD by using PET.
Background:
Neuroinflammation play a significant role in the pathology of Parkinson’s disease (PD). Previous animal and ex-vivo study suggested that zonisamide had beneficial effect against neuroinflammation.
Design/Methods:
Eleven early stage of PD patients and normal controls underwent [11C] DPA713 PET and [11C]CFT PET to assess microglial activation and dopamine transporter density. PD patients were divided into PD with and without zonisamide therapy. All patients were scanned annually for three years (four times per person). The binding potential (BPND) was estimated with simplified reference tissue model. Voxel wised SPM analysis and ROI analysis were used to compare the increase in [11C] DPA713 BPND and [11C]CFT SUVR between two groups. Local association between [11C] DPA713 BPND and [11C]CFT SUVR were evaluated with direct ROI analysis.
Results:
The PD group showed a significant increase in [11C] DPA713 BPND in the whole brain predominantly in the parieto-occipital lobe. Increase in [11C] DPA713 BPND was more broadly in the following scans. The [11C] DPA713 BPND changes were smaller in the zonisamide+ group than in the zonisamide- therapy. Although [11C]CFT SUVR showed chronological decrease in the striatum in all PD group, correlation analysis showed a positive direct correlation between [11C]DPA713 BPND and [11C]CFT SUVR in the putamen in the zonisamide+ group but not in the zonisamide- group. The seven series subtest in MMSE showed significant increase in the zonisamide+ group.
Conclusions:
Microglial activation is present especially over the parieto-occipital cortex even at an early stage of PD. Our in vivo study suggested that zonisamide might have the potential to suppress the neuroinflammation, induce the neuroprotective effect of microglia in the putamen, and beneficial effect on attention.