Saffron Extract Attenuates Anxiogenic Effect and Improves Cognitive Behavior in an Adult Zebrafish Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) has the highest mortality rates worldwide, yet effective treatment remains unavailable. TBI causes inflammatory responses, endoplasmic reticulum stress, disruption of the blood–brain barrier and neurodegeneration that lead to loss of cognition, memory and motor skills. Saffron (Crocus sativus L.) is known for its anti-inflammatory and neuroprotective effects, which makes it a potential candidate for TBI treatment. Zebrafish (Danio rerio) shares a high degree of genetic homology and cell signaling pathways with mammals. Its active neuro-regenerative function makes it an excellent model organism for TBI therapeutic drug identification. The objective of this study was to assess the effect of saffron administration to a TBI zebrafish model by investigating behavioral outcomes such as anxiety, fear and memory skills using a series of behavioral tests. Saffron exhibited anxiolytic effect on anxiety-like behaviors, and showed prevention of fear inhibition observed after TBI. It improved learning and enhanced memory performance. These results suggest that saffron could be a novel therapeutic enhancer for neural repair and regeneration of networks post-TBI.

Assessing Drug Administration Techniques in Zebrafish Models of Neurological Disease

“…A study conducted by Liu et al revealed that retro-orbital venous injection of human umbilical cord perivascular cells in an adult zebrafish model of TBI presented reduced reactive gliosis and apoptosis, and an improvement in locomotor activity and anxiety [243]. An intraperitoneal injection of saffron in a stab wound adult zebrafish model of TBI reversed the cognitive and behavioral deficits observed in lesioned zebrafish [129]. Bath immersion has been used successfully in some studies to deliver drugs to zebrafish models of TBI and stroke.…”

“…One such issue is the limited time frame during which microinjections are the most effective in many cases, which is the one-cell embryonic stage [125]. This, however, no longer becomes an issue when the treatment consists of localized tissue-specific drugs for adult zebrafish in the setting of acquired injury such as TBI [129]. Moreover, microinjection is a procedurally tedious and complex technique, which must be perfected in order to be executed with no damage to the organism being injected.…”