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Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5×105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.

Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms of Parkinson's disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potentials (BAEP), and vestibular evoked myogenic responses (VEMPs) represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular and cervical VEMPs (oVEMPs and cVEMPs) in patients with PD and its correlation to the motor and non-motor symptoms. Fifteen patients diagnosed as idiopathic PD were diagnostic using Unified Parkinson’s Disease Rating Scale (UPDRS) and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale (NMSS). PD patients underwent pure-tone, speech audiometry, and tympanometry, BBAEP, and ocular and cervical VEMPs and compared to fifteen age-matched control subjects. PD subjects showed abnormal BAEPs wave morphology, prolonged absolute latencies of wave V and I-V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEPs and cVEMPs responses contralateral to the clinically more affected (CMA) side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p=0.03 & 0.001), perception (p=0.03), memory / cognition (p=0.025), and urinary scores (p=0.03). The oVEMP responses showed significant correlations to cardiovascular (p= 0.01) and sexual dysfunctions (p=0.013). PD is associated with BAEPs and VEMPs abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features.

Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson’s disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against α-synuclein (α-syn), which is an important protein involved in the pathogenesis of PD. In our study patients with PD (46 patients), Alzheimer’s disease (AD) (27 patients) and healthy controls (20 patients) were evaluated according to their sera α-syn AIAs levels. Interestingly, α-syn AIAs were significantly elevated in PD group compared to AD and healthy controls, which advocates their use for diagnosis of PD.