Research PaperRefining environmental enrichment to advance rehabilitation based research after experimental traumatic brain injury
Introduction
The World Health Organization predicts that traumatic brain injuries (TBI) will become the leading cause of death and disability by the year 2020 (Hyder et al., 2007). Through many convoluted mechanisms including both the injury caused by the primary initial impact and the damaging secondary and tertiary pathophysiological cascades that follow (Kline et al., 2016, Adelson et al., 1998, Bayir et al., 2009, Bramlett et al., 2016, Carlson et al., 2017), TBIs induce a wide variety of long-lasting symptoms including motor deficiencies (Kline et al., 1994, Blaya et al., 2014, Shear et al., 2015), disrupted cognitive function (Horneman and Emanuelson, 2009, Levin et al., 2010, Barry and Tomes, 2015, Richter et al., 2015), and fatigue (LaChapelle and Finlayson, 1998). While public awareness has increased regarding the dangers of TBI, the affective and economic costs of TBIs remain astronomical and effective treatment strategies are scarce (Doppenberg et al., 2004, Menon, 2009). However, promoting recovery of motor and cognition and managing fatigue continue to be primary concerns of health specialists as they strive to assimilate patients back into society.
Neurorehabilitation and its rodent analogue environmental enrichment (EE) have both been successful in conferring robust benefits after TBI (Chua et al., 2007, de Witt et al., 2011, Bondi et al., 2014, Radabaugh et al., 2016, Hart et al., 2016). Clinical rehabilitative treatments employ a transdisciplinary team of specialists to target multiple different aspects of each unique injury resulting in the patient being exposed to a wide variety of stimuli (Chua et al., 2007). However, with 29% to 47% of TBI patients reporting abnormal levels of fatigue within the first month after injury (Minderhoud et al., 1980), longer rehabilitation sessions may prove to be less productive as the fatigue becomes distracting or unbearable (Keshaven et al., 1981, LaChapelle and Finlayson, 1998). Hence, multiple shorter sessions of rehabilitation may ease fatigue and afford more productive rehabilitation efforts as well as increased interaction with the stimuli.
EE mimics many of the stimuli patients are exposed to in the clinic by encouraging voluntary exercise, increasing social interaction, and providing cognitive stimulation. While the stimuli are analogous to the clinic, the typically used paradigm, which consists of continuous exposure after TBI (Radabaugh et al., 2016, de Witt et al., 2011, Monaco et al., 2014, Sozda et al., 2010, Kline et al., 2007, Bondi et al., 2014, Bondi et al., 2015) is quite dissimilar as patients do not receive rehabilitation on a continual basis. Previous studies have observed the effects of abbreviated EE after experimental TBI and reported that both male (de Witt et al., 2011) and female (Radabaugh et al., 2016) rats benefit from 6-hrs of EE exposure per day. Indeed, the benefits conferred by the 6-hr EE paradigm are not significantly different from the continuous approach. While patients in the clinic may spend up to 6-hrs participating in neurorehabilitation each day, it is often in multiple, shorter sessions that target different aspects of the recovery process (i.e., speech therapy, vocational therapy, exercise) (Chua et al., 2007). Therefore, progressive experimental manipulations to the typical EE paradigm could continue to refine EE and advance rehabilitation based research.
This study aimed to evaluate the effects generated by two 3-hr sessions of EE exposure each day compared to one 6-hr session. We hypothesized that the group receiving two shorter sessions of EE per day would recover more fully, as measured by well-established motor and cognitive tasks, than the one receiving one 6-hr session of EE. The rationale for the hypothesis is that rats placed into the EE cage twice per day and given a rest period will not be as negatively impacted by fatigue and may acclimate less to the environment thus promoting more interaction with the “novel” stimuli when reintroduced for the second session. This increased amount of engagement could provide further benefit from the rehabilitation and potentially lead to a greater degree of cognitive flexibility and motor ability. Support for this thesis comes from the work of Sozda et al. (2010) who showed that atypical EE groups, which had one of the critical components of EE (i.e., physical space, cognitive stimuli, or social interaction) excluded, did not recover to the same degree as those in the typical EE groups, indicating that exploration and engagement are important.
Section snippets
Subjects and pre-surgical procedures
Fifty-one adult male Sprague-Dawley rats (Harlan, Indianapolis, Indiana) were paired in ventilated polycarbonate rat cages and maintained in a temperature (21 ± 1 °C) and light (on 0700–1900 h) controlled environment with food and water available ad libitum. During the week of acclimatization the rats were pre-trained on the beam-walk task to ensure that they could traverse the entire length of the beam effortlessly, typically in under 5 s. On the morning of surgery, the rats were pre-assessed on
Results
There were no significant differences in any assessment among the sham control groups, regardless of housing condition, and thus the data were pooled into a single SHAM group.
Discussion
Numerous studies have shown that environmental enrichment (EE), a rodent analogue of rehabilitation, confers significant motor, cognitive, and histological benefits after experimental brain injury in both male and female rodents (Hamm et al., 1996, Passineau et al., 2001, Hicks et al., 2002, Kline et al., 2007, Sozda et al., 2010, de Witt et al., 2011, Bondi et al., 2014, Monaco et al., 2014, Radabaugh et al., 2016, Zeleznikow-Johnston et al., 2017). While the majority of the EE studies have
Acknowledgements
This work was supported, in part, by NIH grants HD069620, HD069620-S1, NS060005, NS084967 (AEK), NS094950, NS099683 (COB), the University of Pittsburgh Physicians/UPMC Academic Foundation, and the UMPC Rehabilitation Institute (COB).
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