Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats

Abstract

Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and antiapototic effects.

Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats

“…Both neurotrophins (BDNF and NGF) are implicated with spinogenesis and increase dendritic arbor (Adams et al, ; Kolarow, et al, ). According to our results, a recent report has demonstrated that Cbl may reduce high levels of NO and increase low levels of glutamate content in the hippocampus of streptozotocin‐induced hyperglycemia, an animal model of diabetes mellitus (Georgy et al, ). Finally, our recent reports in aged animals demonstrated that Cbl increases the dendritic arbor and dendritic spine density of the pyramidal neurons of the CA1 and DG of the dorsal hippocampus and layer 3 and 5 of the PFC (Alcantara‐Gonzalez et al, ; Juárez et al, ).…”

Consequences of diabetes mellitus on neuronal connectivity in limbic regions

“…Currently, as mentioned before, patients with DM who have exhibited a chronic increase in glycemic blood levels (hyperglycemia) have shown changes in the brain, such as a reduced size of the PFC and the hippocampus with cognitive deficits in declarative memory (Bruehl et al, ; Kerti et al, ; van Bloemendaal et al, ; Yang et al, ; Zhang et al, ; Zhou et al, ). Moreover, recent reports in animal models with DM‐induced by streptozotocin have shown that continuous hyperglycemia leads to damage at the neuronal level (Georgy, et al, ; Lazcano et al, ; Martinez‐Tellez et al, ; Sanchez‐Vega et al, ; Shingo et al, ). High levels of glycemia may produce dendritic atrophy with a reduced number of dendritic spines at the level of pyramidal neurons of the PFC and the hippocampus in the rats (Brocca et al, ; Joghataie et al, ; Lazcano et al, ; Martinez‐Tellez et al, ; Shingo et al, ; Xiang et al, ) and mice (Beauquis et al, ; Malone et al, ; Sanchez‐Vega et al, ; Taylor et al, ) (see Table ).…”

Neurotrophic and antioxidant potential of neuropeptides and trace elements

“…Церебролизин потенцирует когнитивную функцию на моделях сахарного диабета, уменьшая уровень провоспали-тельного фактора (фактор некроза опухоли α), повышая уровень инсулиноподобного гормона роста (IGF-1), серо-тонина и оказывая антиоксидантное действие на нейроны головного мозга [35].…”

“…Под влиянием церебролизина улучшается восстанов-ление когнитивных способностей после легкой ЧМТ, в ча-стности за счет стимулирования ангиогенеза и быстрого восстановления поврежденной нейрональной сети [35]. Улучшение неврологического состояния при использова-нии церебролизина после экспериментального сотрясения мозга сопровождалось восстановлением целостности аксо-нов в полосатом теле.…”