The present study demonstrates the neuroprotective potential of Vinpocetine against weight drop induced traumatic brain injury (TBI) in rats. Currently used weight drop model was described by Marmarou et al and represents the most widely used model to mimic the real life TBI. TBI generally impacts the whole brain but the vulnerable areas are frontal and temporal lobes which is clearly observed by (Schwarzbold et al. 2010) which impairs the cognitive and motor performance which could be co-related with our findings in behavioural parameters.
Herein the current study, weight drop induced TBI caused significant decrease in body weight, spontaneous locomotor activity. The decline in body weight may be correlated with the associated hypermetabolic response causing elevation in resting energy expenditure which ultimately results in weight loss (Charrueau et al. 2009) and may be due to both peripheral and central effects. To understand the severity of the injury the animals were subjects to a battery of parameters including OFT, rotarod & ORT. Spontaneous locomotor activity is an important parameter to relate basal ganglionic functions which are observed by OFT while Grip strength is estimated by rotarod which also depicts motor learning. Both parameters are important as already mentioned they indicate the severity of the injury and were found to be affected as they showed maximum passive time, least number of crossings in OFT and decreased fall off time in rotarod.
The other important parameter we have performed is ORT which purely indicates the cognitive impairment. According to various findings it is well proved that TBI destruct hippocampus & cortex (Dempsey and Rao 2003; Xiong et al. 2014) which may be correlated with the poor performance of the traumatized rats in ORT in which they are unable to discriminate between familial and novel objects also evidenced by other findings confirming the associated cognitive impairment (Kaur et al. 2018). These observed findings in behavioural parameters confirm the induction of brain injury. As already stated brain injury can trigger activation of various deleterious pathways which ultimately result in neurodegenerative changes. Here in current study vinpocetine treatment through its multihit properties dose dependently attenuated locomotor and cognitive functions of traumatized rats also supported by many studies in various models (Zaitone, Abo-Elmatty and Elshazly, 2012, Deshmukh and Sharma, 2013; Sharma and Deshmukh, 2015).
Communication between neurons at synaptic junctions is an elegant process that facilitates the transmission of various electro-chemical signals in the central nervous system. According to previous findings alterations in synaptic transmission across synapses have been associated with motor and cognitive impairment (Deshmukh and Sharma 2013; Sharma and Deshmukh 2015). There are various neurotransmitters which maintain locomotor activity such as dopamine (DA), serotonin (5-HT), norepinephrine (NE) and acetylcholine (ACh). Among them, DA, NE and 5-HT are considered to play major role in locomotion. Frontal lobes are enriched with dopamine, brain injury is known to produce a decline in synaptic monoaminergic neurotransmission due to its destruction also evidenced by some findings (Kaur et al. 2018; Rashno et al. 2019). It has been reported that the level of norepinephrine and serotonin found to be declined due to their increased metabolism (PEIRCE 2000). Brain injury produced a significant decrease in overall monoaminergic transmission levels and can be well co-related with the observed motor deficits rats. In contrast, vinpocetine significantly elevates the levels of monoamines towards normal and improves the locomotor activity. Vinpocetine elevate cyclic nucleotide levels (Deshmukh et al. 2009b) ,as discussed before, cyclic nucleotides known to improve central neurotransmitters including monoamines and basal ganglionic functions (Sharma and Deshmukh 2015). Results obtained are in line with the recent studies demonstrating increased striatal dopamine, serotonin and norepinephrine levels following vinpocetine treatment in other model systems in rats (Kaur et al. 2018; Rashno et al. 2019). Thus, observed improvement in motor functions following vinpocetine treatment in TBI rats may be due to restoration of monoamine levels in traumatized rat brains which can be well correlated with the improvement in OFT and rotarod performance. Another important neurotransmitter ACh that majorly plays a major role in arousal, memory, locomotion and other functions. In the periphery, besides its role in parasympathetic function, it is the major transmitter innervating somatic muscles. Not surprisingly, peripheral dysfunction produces motor impairment and central dysfunction can produce both alterations in states of consciousness e.g., sleep and memory function (PEIRCE 2000). Brain injury spikes up the AChE activity which could relate to ACh levels in the current study. AChE is an enzyme involved in the metabolism of ACh into acetate and choline. Our TBI induced rats showed elevation in AChE activity is in line with the other finding (Wang and Zhang 2018). On the contrary, vinpocetine treatment significantly and dose dependently attenuated elevated AChE activity in traumatized rats hence result in better locomotion and cognitive functioning.
TBI is known to trigger the various pathogenetic mechanisms such as excitotoxicity, voltage gated sodium channels dysregulation, apoptosis, and cerebral dysfunctioning which elevates the production of reactive oxygen species. A growing body of evidences implicates the destructive role of oxidative & nitrosative stress followed by brain injury (Attella et al. 1989; Okigbo et al. 2019; Rashno et al. 2019; Ali et al. 2020). Secondary injury cascade initiates imbalance between the ROS and the endogenous antioxidant system contributing in the oxidative stress (Wu et al. 2006). The present study showed the increased lipid peroxidation, nitrite levels, and altered endogenous antioxidant defence system in traumatized rats. TBI rats indicated a decrease in levels of glutathione peroxidase (GSH), catalase and superoxide dismutase (SOD). Vinpocetine significantly attenuated oxidative stress in TBI rats and restored anti-oxidant enzyme levels towards normal. Vinpocetine known to improve cerebral glucose utilization and up regulate the anti-oxidant enzymatic activities and can scavenge free radicals via its anti-oxidant, anti-excitotoxicity, and anti-inflammatory activities (Jha et al. 2012; Deshmukh and Sharma 2013; Ali et al. 2020).
Thus we can conclude that vinpocetine tends to improve locomotor functions, cognitive impairment, neurochemical, and biochemical alterations induced by weight drop model. Vinpocetine has the potential to maintain neurochemical balance, cholinergic functions, and attenuates the increased oxidative stress. Although further studies need to be done to explore the molecular mechanisms involved in the neuroprotective potential of vinpocetine against weight drop induced impairment.