Environmental enrichment improves traumatic brain injury-induced behavioral phenotype and associated neurodegenerative process

Tapias, Vı́ctor; Moschonas, Eleni H.; Bondi, Corina O.; Vozzella, Vincent J.; Cooper, Iya N.; Cheng, Jeffrey P.; Lajud, Naima; Kline, Anthony E.

doi:10.1016/j.expneurol.2022.114204

Cited by 25 publications

(12 citation statements)

References 58 publications

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“…In this study, SB332235 was capable of ameliorating the neuronal damage and improved subsequent motor and cognitive de cits at 3 days post-injury. In parallel with previous studies [26, [33][34][35], our data showed that TBI caused pronouncedly higher mNSS score, reduction of time to maintain balance in beam-balance, enhancement in ambulatory time and a concomitant diminution in resting time in an open eld, and reduced discrimination index in novel object recognition task in animals, suggesting that TBI can trigger neurological de ciency, motor, and cognitive dysfunction. Of particular noteworthy, treatment with SB332235 potently reversed such de cits as shown by the lower mNSS score, elevation of time to maintain balance, decrease in ambulatory time and increase in resting time, and enhancement of discrimination index in TBI-exposed animals, indicative of a bene cial effect of SB332235 on the motor and memory impairments.…”

Section: Discussionsupporting

confidence: 90%

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Zhao

Zhou

Gou

et al. 2023

Preprint

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The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered 30 min after TBI, followed by additional doses at 6, 24, and 30 hours. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

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Section: Discussionsupporting

confidence: 90%

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Zhao

Zhou

Gou

et al. 2023

Preprint

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“…Initially, we observed that the studies used different species of rodents (rats and mice). Five studies used Sprague Dawley rats ( Fernández et al, 2004 ; Jain et al, 2012 ; Zhang et al, 2016 , 2021 ; Tapias et al, 2022 ). Five studies used Wistar rats ( Pereira et al, 2009 ; Cechetti et al, 2012 ; Prado Lima et al, 2018 ; Molina et al, 2021 ; Thamizhoviya and Vanisree, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…One study used Kunming mice ( Cheng et al, 2014 ), and one study used TgCRND8 mice ( Herring et al, 2010 ). Regarding gender, 10 included studies used male individuals only ( Pereira et al, 2009 ; Cechetti et al, 2012 ; Jain et al, 2012 ; Zhang et al, 2016 , 2021 ; Mármol et al, 2017 ; Prado Lima et al, 2018 ; Montes et al, 2019 ; Thamizhoviya and Vanisree, 2021 ; Tapias et al, 2022 ). Five studies used both sexes ( Fernández et al, 2004 ; Cheng et al, 2014 ; Mármol et al, 2015 ; Muhammad et al, 2017 ; Molina et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…In the hippocampus, three studies observed a decrease in DCF after exposure to EE associated with chronic cerebral hypoperfusion, noise, and oxidative damage (Cechetti et al, 2012;Molina et al, 2021;Thamizhoviya and Vanisree, 2021). Two studies showed no significance in DCF levels after EE (Prado Lima et al, 2018;Tapias et al, 2022) (Table 4).…”

Section: Environmental Enrichment On Oxidative Stress Biomarkers In B...mentioning

confidence: 99%

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The impact of enriched environments on cerebral oxidative balance in rodents: a systematic review of environmental variability effects

Ramos,

de Sousa Fernandes,

da Silva Fidélis

et al. 2024

Front. Neurosci.

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IntroductionThe present review aimed to systematically summarize the impacts of environmental enrichment (EE) on cerebral oxidative balance in rodents exposed to normal and unfavorable environmental conditions.MethodsIn this systematic review, four databases were used: PubMed (830 articles), Scopus (126 articles), Embase (127 articles), and Science Direct (794 articles). Eligibility criteria were applied based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) strategy to reduce the risk of bias. The searches were carried out by two independent researchers; in case of disagreement, a third participant was requested. After the selection and inclusion of articles, data related to sample characteristics and the EE protocol (time of exposure to EE, number of animals, and size of the environment) were extracted, as well as data related to brain tissues and biomarkers of oxidative balance, including carbonyls, malondialdehyde, nitrotyrosine, oxygen-reactive species, and glutathione (reduced/oxidized).ResultsA total of 1,877 articles were found in the four databases, of which 16 studies were included in this systematic review. The results showed that different EE protocols were able to produce a global increase in antioxidant capacity, both enzymatic and non-enzymatic, which are the main factors for the neuroprotective effects in the central nervous system (CNS) subjected to unfavorable conditions. Furthermore, it was possible to notice a slowdown in neural dysfunction associated with oxidative damage, especially in the prefrontal structure in mice.DiscussionIn conclusion, EE protocols were determined to be valid tools for improving oxidative balance in the CNS. The global decrease in oxidative stress biomarkers indicates refinement in reactive oxygen species detoxification, triggering an improvement in the antioxidant network.

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“…We suggest that such correlations may have predictive value for obtaining early estimates of long-term damage, and potentially informing the optimal treatments. In addition to pharmacological interventions, enriched environments with monitored exercise 107–109 and virtual environments are deemed helpful during chronic TBI recovery in rodents 110 and humans 111, 112 , including virtual social networks. 113 Future investigations, in addition to assessing influence of sex should investigate how vascular smooth muscle attributes are modified by TBI 114 and how pericytes regulate blood flow.…”

Section: Discussionmentioning

confidence: 99%

Delayed cerebrovascular dysfunction and social deficits after traumatic brain injury

Singh,

Gong,

et al. 2024

Preprint

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Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. Acute TBI modifies neurovascular physiology and behavior but a gap in our understanding are the chronic physiological implications of altered brain perfusion on behavioral activities, particularly social interactions.We investigated longitudinal functional vascular networks across the brain for 2-months post- TBI and its impact on social behavior. Adult C57/BL6 male mice received a moderate cortical TBI. Behavior (foot-fault, open-field, 3-chamber social preference) was assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi) followed by magnetic resonance imaging (MRI, 9.4T). Anatomical MRI (T2-weighted), dynamic susceptibility contrast (DSC) perfusion weighted MRI (PWI) were acquired at each temporal epoch. After the final 60dpi MRI, animals underwent transcardial perfusion fixation to map angioarchitecture. MRI data were analyzed using standardized protocols followed by cross-correlations between social behavior, cerebral perfusion, and vascular metrics.Social behavior deficits at 60dpi emerged as reduced interaction with a familiar cage-mate (partner). We observed multiphasic decrements in cerebral blood flow (CBF) encompassing lesion and perilesional cortex where acute reductions at 3-14dpi partially recovered by 30dpi, followed by significant reductions in perfusion at 60dpi. The CBF perturbations extended antero-posteriorly from the ipsilateral TBI impact site but also adulterated contralateral brain regions. CBF reductions impacted regions known to regulate social behavior including hippocampus, hypothalamus, and rhinal cortex. Alongside perfusion deficits at 60dpi, social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interaction.Thus, the novel temporal neurovascular loss, and subsequent recovery followed by chronic decrements are broadly reflected by social interaction perturbations. Our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions, where early evaluation can potentially predict long-term outcomes. Thus, our study provides a clinically relevant timeline of alterations in functional vascular recovery that can guide research for future therapeutics.

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Environmental enrichment improves traumatic brain injury-induced behavioral phenotype and associated neurodegenerative process

Cited by 25 publications

References 58 publications

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome

The impact of enriched environments on cerebral oxidative balance in rodents: a systematic review of environmental variability effects

Delayed cerebrovascular dysfunction and social deficits after traumatic brain injury

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