Regulatory and autoregulatory physiological dysfunction as a primary characteristic of post concussion syndrome: Implications for treatment

Leddy, John J.; Kozlowski, Karl F.; Fung, Michael; Pendergast, David R.; Willer, Barry

doi:10.3233/nre-2007-22306

Cited by 157 publications

(79 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study fits well with the ABCDE (Awakening and Breathing Co-ordination, Delirium monitoring and Exercise/Early mobility) model used in the intensive care setting for prevention of brain dysfunction (Vasilevskis et al 2010). We concur with the general recommendation in clinical practice that concussion patients should rest until they are asymptomatic (Leddy et al 2007), but once they reach this stage we believe that a proper exercise intervention programme should be initiated. Such interventions could provide significant benefits and dramatically reduce patients' recovery period, as seen in our model.…”

Section: Discussionsupporting

confidence: 83%

“…Although exercise exerts many beneficial effects on the brain, including the promotion of neuronal repair (Vaynman & Gomez-Pinilla, 2005) and inhibition of neuroinflammation (Leem et al 2011), the effects of exercise in animal studies of traumatic brain injury have been controversial (McCrea et al 2009). Moreover, most postconcussion patients are advised not to exercise because of concerns regarding exacerbation of symptoms (Leddy et al 2007). We have shown that exercise improves learning and memory (Huang et al 2006;Liu et al 2009) and enhances neuroprotective effects against brain degeneration (Wu et al , 2011.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Early postinjury exercise reverses memory deficits and retards the progression of closed‐head injury in mice

Chen

Huang²,

Kuo

et al. 2013

The Journal of Physiology

View full text Add to dashboard Cite

Key points• Exercise benefits the brain in many ways, e.g. promoting neuron repair and inhibiting neuroinflammation. However, current clinical practices often advise patients suffering head injury to rest during the post-traumatic period.• This study used a mouse model to investigate whether and how exercise retarded the brain structural and functional losses induced by a head impact.• An early moderate-exercise protocol (starting 2 days postimpact and lasting for 7 or 14 days) reversed the impact-induced rapid loss of recognition memory and prevented most of the delayed neuronal loss and neuroinflammation.• However, the same exercise protocol started 9 days postimpact was unable to restore deficits in the recognition memory, even though it still retarded the late-phase neuroinflammation.• These beneficial effects of exercise were probably mediated by the timely recovery of neurotrophic factors (brain-derived neurotrophic factor and mitogen-activated protein kinase phosphatase-1) in the injured brain.Abstract Closed-head injury (CHI) usually involves both physical damage of neurons and neuroinflammation. Although exercise promotes neuronal repair and suppresses neuroinflammation, CHI patients currently often remain resting during the post-traumatic period. This study aimed to investigate whether and how postinjury exercise benefited the brain structure and function in mice after CHI. Closed-head injury immediately caused an elevated neurological severity score, with rapid loss of object recognition memory, followed by progressive location-dependent brain damage (neuronal loss and activation of microglia in the cortex and hippocampus). An early exercise protocol at moderate intensity (starting 2 days postimpact and lasting for 7 or 14 days) effectively restored the object recognition memory and prevented the progressive neuronal loss and activation of microglia. However, if the exercise started 9 days postimpact, it was unable to recover recognition memory deficits. In parallel, early exercise intervention drastically promoted neurite regeneration, while late exercise intervention was much less effective. We also tested the possible involvement of brain-derived neurotrophic factor (BDNF) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in the exercise-induced beneficial effects. Exercise gradually restored the impact-abolished hippocampal expression of BDNF and MPK-1, while oral administration of triptolide (a synthesis inhibitor of MKP-1 and an antagonist of nuclear factor-κB) before each bout of exercise blocked the restorative effects of exercise on MKP-1 and recognition memory, as well as the exercise-induced retardation of neuronal loss. Although triptolide treatment alone inhibited activation of microglia and maintained neuronal numbers, it did not recover the injury-hampered recognition memory. Overall, moderate exercise

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 98%

Early postinjury exercise reverses memory deficits and retards the progression of closed‐head injury in mice

Chen

Huang²,

Kuo

et al. 2013

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Post‐TBI autonomic dysfunction has been proposed as a possible cause for prolonged symptoms of PCS [20]. In studies of moderate to severe TBI, altered ANS regulation is believed to be due to changes in the autonomic centers in the brain and/or an uncoupling of the connections between the central ANS, the arterial baroreceptors, and the heart [21], is proportional to TBI severity, and improves with TBI recovery [21].…”

Section: The Physiology Of Concussionmentioning

confidence: 99%

The Role of Controlled Exercise in Concussion Management

Leddy

Hinds

Sirica

et al. 2016

PM&R

Self Cite

129

View full text Add to dashboard Cite

Concussion affects the autonomic nervous system and its control of cerebral blood flow, which may be why uncontrolled activity can exacerbate symptoms after concussion. Traditionally, patients have been advised to restrict physical and cognitive activity until all symptoms resolve. However, recent research suggests that prolonged rest beyond the first couple of days after a concussion might hinder rather than aid recovery. Humans do not respond well to removal from their social and physical environments, and sustained rest adversely affects the physiology of concussion and can lead to physical deconditioning and reactive depression. Some animal data show that early forced exercise is detrimental to recovery after concussion, but other animal data show that voluntary exercise is not detrimental to recovery. We developed the Buffalo Concussion Treadmill Test to systematically evaluate exercise tolerance in persons with prolonged symptoms after concussion (ie, more than 4-6 weeks, which is called postconcussion syndrome [PCS]). Using a predetermined stopping criterion (symptom-exacerbation threshold), akin to voluntary exercise in animals, the Buffalo Concussion Treadmill Test is the only functional test known to safely and reliably reveal exercise intolerance in humans with PCS. The test data are used to develop individualized subthreshold exercise treatment programs to restore the physiology to normal and enhance recovery. Return of normal exercise tolerance can then be used to establish physiological recovery from concussion. New research suggests that absolute rest beyond the first few days after concussion may be detrimental to concussion recovery. However, further research is required to determine the appropriate mode, duration, intensity, and frequency of exercise during the acute recovery phase of a concussion prior to making specific exercise recommendations. For patients with PCS, subsymptom threshold exercise improves activity tolerance and is an appropriate treatment option for this patient population.

show abstract

“…Thus, it is critical to know the time of day when individuals are tested so that any follow-up testing can be carried out at the same time to ensure that the data being collected are physiologically appropriate to compare (Burton et al, 2010;Shaffer et al, 2014). This is especially important when considering concussion as there are changes in circadian rhythm that coincide with the injury (Leddy et al, 2007). Additionally, it is important that any matched control participants being tested against a concussed individual do so at the same time of day.…”

Section: Concussion and Hrvmentioning

confidence: 99%

Heart rate variability and implication for sport concussion

Bishop

Dech

Guzik

et al. 2017

Clin Physio Funct Imaging

View full text Add to dashboard Cite

Finding sensitive and specific markers for sports-related concussion is both challenging and clinically important. Such biomarkers might be helpful in the management of patients with concussion (i.e. diagnosis, monitoring and risk prediction). Among many parameters, blood flow-pressure metrics and heart rate variability (HRV) have been used to gauge concussion outcomes. Reports on the relation between HRV and both acute and prolonged concussion recovery are conflicting. While some authors report on differences in the low-frequency (LF) component of HRV during postural manipulations and postexercise conditions, others observe no significant differences in various HRV measures. Despite the early success of using the HRV LF for concussion recovery, the interpretation of the LF is debated. Recent research suggests the LF power is a net effect of several intrinsic modulatory factors from both sympathetic and parasympathetic branches of the autonomic nervous system, vagally mediated baroreflex and even some respiratory influences at lower respiratory rate. There are only a few well-controlled concussion studies that specifically examine the contribution of the autonomic nervous system branches with HRV for concussion management. This study reviews the most recent HRV- concussion literature and the underlying HRV physiology. It also highlights cerebral blood flow studies related to concussion and the importance of multimodal assessment of various biological signals. It is hoped that a better understanding of the physiology behind HRV might generate cost-effective, repeatable and reliable protocols, all of which will improve the interpretation of HRV throughout concussion recovery.

show abstract

Regulatory and autoregulatory physiological dysfunction as a primary characteristic of post concussion syndrome: Implications for treatment

Cited by 157 publications

References 72 publications

Early postinjury exercise reverses memory deficits and retards the progression of closed‐head injury in mice

Early postinjury exercise reverses memory deficits and retards the progression of closed‐head injury in mice

The Role of Controlled Exercise in Concussion Management

Heart rate variability and implication for sport concussion

Contact Info

Product

Resources

About