Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation

(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (−26 ± 1.9 µm and −52 ± 2.8 µm, p < 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10(−7) M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (−26 ± 2.3% and −31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and −16 ±2.5%). The TP receptor agonist U46619 (10(−7) M) elicited substantial constrictions of MCA from intact rats (−21 ± 3.3%), which were also significantly reduced, after TBI (to −16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors

Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats

Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI

A gastrooesophagealis refluxban szenvedő betegek elégedettségének felmérése | Patient satisfaction with care in gastrooesophageal reflux disease

Bevezetés: A betegségek kezelésében a gyógyszeres terápia alkalmazása mellett fontos az orvos–beteg partneri viszonyt megalapozó kommunikáció. Célkitűzés: Annak a felderítése, hogy a beteg milyen kapcsolatot tud kialakítani kezelőorvosaival, valamint az ellátórendszerrel való elégedettségét mi határozza meg. Módszer: Gastrooesophagealis reflux miatt gondozott betegeket (n = 80) az ellátás szintjei alapján falusi (n = 20), pécsi (n = 20) és komlói (n = 20) háziorvosok betegei, valamint szakorvosok betegei (n = 20) csoportokba osztották. A betegek orvosukkal való kapcsolatának személyes voltára, a közöttük levő kommunikációra, a betegek elégedettségére vonatkozó kérdéseket tettek fel. Eredmények: Személyes problémával a betegek közel 80%-a kereste már háziorvosát, szemben szakorvosával (20%; p < 0,001). Háziorvosi rendelőkben a betegek elégedettebbek a betegségről kapott tájékoztatással (95%), mint a szakrendelőben (65%; p = 0,002). A háziorvosi rendelőkben több beteg nyilatkozta, hogy elegendő időt fordítottak rá (96,7%; 80%; p = 0,032). Következtetések: A betegek háziorvosukkal könnyebben kommunikálnak, közöttük közvetlenebb a kapcsolat. A mélyebb személyes viszony a háziorvosi praxisban gondozott betegek sikeres kezelésének záloga. Orv. Hetil., 2013, 154, 1713–1718. | Introduction: Besides medical treatment, adequate communication and personal relationships between physicians and patients are the most important determinants of patient satisfaction. Aim: To explore doctor–patient relationships, and factors that may determine patient satisfaction with care. Method: Patients with gastroesophageal reflux (n = 80) were divided into subgroups treated by family doctors or by gastroenterologists. Patients were asked to fill in a questionnaire about communication and patient satisfaction. Results: Significantly more patients visited family doctors than gastroenterologists with health problems (80%; 20%, p < 0.001). Patients were significantly more satisfied with the information they received about the process of care provided by family doctors (95%) compared to that they obtained from gastroenterologists (65%; p = 0.002). Significantly more patients in family practices indicated that their doctors spent enough time with them compared to subspecialists (96.7%; 80% p = 0.032). Conclusions: Patients develop a closer personal relationship and more appropriate communication with family doctors compared to specialists, which can be an important component of successful treatment. Orv. Hetil., 154 (43), 1713–1718

Hypertension-Induced Enhanced Myogenic Constriction of Cerebral Arteries Is Preserved after Traumatic Brain Injury

Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue from pressure/volume overload; however, it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels. We hypothesized that in hypertensive rats, the enhanced myogenic cerebrovascular response is preserved after TBI. Therefore, we investigated the myogenic responses of isolated middle cerebral arteries (MCA) of normotensive and spontaneously hypertensive rats (SHR) after severe impact acceleration diffuse brain injury. TBI diminished myogenic constriction of MCAs isolated from normotensive rats, whereas the 20-HETE-mediated enhanced myogenic response of MCAs isolated from SHRs was not affected by TBI. These results suggest that the optimal cerebral perfusion pressure values and vascular signaling pathways can be different and, therefore, should be targeted differently in normotensive and hypertensive patients following TBI

The effect of mild traumatic brain injury on cerebral microbleeds in aging

Traumatic brain injury (TBI) induces the formation of cerebral microbleeds (CMBs), which are associated with cognitive impairment, psychiatric disorders and gait dysfunction in patients. Elderly people frequently suffer TBI, especially mild brain trauma (mTBI). Interestingly, aging is an independent risk factor for the development of CMBs, as well. However, it is not well established how TBI and aging may interact to promote the development of CMBs. In order to test the hypothesis that mild TBI exacerbates the development of CMBs in the elderly we compared the number and cerebral distribution of CMBs assessed by analysing susceptibility weighted (SWI) magnetic resonance imaging (MRI) in young (25 +/- 10 year-old, n=18) and elder (72 +/- 7 year-old, n=17) patients after mTBI and in aged matched healthy subjects (young: 25 +/- 6 year- old, n=20; aged: 68 +/-5 year-old, TBI and aging-induced CMB 11 This is a provisional file, not the final typeset article n=23). We found significantly more CMBs in elder patients after mTBI compared to young patients, however, we did not observe a significant difference in the number of cerebral microhemorrhages between aged and aged + mTBI patients. The majority of CMBs were found supratentorially (lobar and basal ganglion). Lobar distribution of supratentorial CMBs showed that aging enhances the formation parietal and occipital CMBs after mTBI. This suggests that aging and mTBI do not synergize in the induction of the development of cerebral microbleeds and that different distribution of mTBI induced CMBs in aged patients may lead to specific age-related clinical characteristics of mTBI

Effect of Growth Hormone on Neuropsychological Outcomes and Quality of Life of Patients with Traumatic Brain Injury: A Systematic Review

One of the most devastating chronic consequences of traumatic brain injury (TBI) is cognitive impairment. One of the possible underlying causes is growth hormone deficiency (GHD) caused by TBI-induced hypopituitarism. Currently, TBI patients are not routinely screened for pituitary function, and there are no standard therapies when GHD is diagnosed. Further, the possible positive effects of GH replacement on cognitive function and quality of life after TBI are not well established. We aimed to assess the current knowledge regarding the effect of GH therapy on cognitive function and quality of life after TBI. We performed a literature search in PubMed, Embase, and Central(®) databases from inception to October 2019. We extracted data on each term of severity (mild-moderate-severe) of TBI with and without GHD, time since injury, parameters of growth hormone treatment (dosing, length), and cognitive outcomes in terms of verbal and non-verbal memory, and executive, emotional, and motor functions, and performed a meta-analysis on the results of a digit span test assessing working memory. We identified 12 studies (containing two randomized controlled trials) with 264 mild-to-moderate-to-severe TBI patients (Glasgow Coma Score [GCS] varied between 6 and 15) with (n = 255) or without (n = 9) GHD who received GH therapy. GH was administered subcutaneously in gradually increasing doses, monitoring serum insulin-like growth factor-I (IGF-I) level. After TBI, regardless of GCS, 6–12 months of GH therapy, started in the chronic phase post-TBI, induced a moderate improvement in processing speed and memory capacities, decreased the severity of depression, and led to a marked improvement in quality of life. Limitations include the relatively low number of patients involved and the divergent neuropsychological tests used. These results indicate the need for further multi-centric controlled studies to substantiate the use of GH replacement therapy as a potential tool to alleviate TBI-related cognitive impairment and improve quality of life