3. List of proposed parameters can be evaluated on the basis of behavioral and biochemical alterations in neurotoxic experimental animal models of autism

Proposed experimental design of propionic acid-induced behavioral and biochemical estimations (Figure 3)


2.1. Propionic acid and autism

8 Recent Advances in Neurodegeneration

Figure 1. PPA-induced neurotoxicity; selective mitochondrial inhibition.

Propionic acid (PPA) is a short chain fatty acid formed endogenously in the human body as an intermediate of fatty acid metabolism and a metabolic end product of enteric gut micro biota such as clostridia and propionic bacteria [43–46]. MacFabe et al. and Shultz et al. have demonstrated that PPA intraventricularly infused to rats provides a suitable animal model to study autism. Being a weak organic acid, PPA exists in ionized and nonionized forms at physiological pH allowing it to readily cross lipid membranes, including the gut-blood and blood-brain barriers. PPA and other short-chain fatty acids (i.e., butyrate and acetate), affect diverse physiological processes such as cell signaling, neurotransmitter synthesis and release, mitochondrial

Figure 2. Intraventricular injection of PPA-inducing neurotoxic effect in mitochondrial respiratory chain (ETC).

Spatial navigation task in Morris water maze, spontaneous locomotor activity, string test for grip strength, elevated plus maze test, beam crossing task, force swim test, rota rod apparatus

4. Estimation of biochemical parameters

Preparation of homogenate, estimation of biochemical parameters in serum and tissue homogenate such as protein estimation, lactate dehydrogenase (LDH) assay, estimation of malondialdehyde (MDA) levels, glutathione levels, superoxide dismutase (SOD) activity, catalase activity, acetyl cholinesterase (AChE) levels, determination of protein carbonyl (PC), nitrite levels

5. Estimation of biochemical parameters in serum and urine

Estimation of total urea, estimation of uric acid, estimation of biochemical parameters in tissue homogenate for mitochondrial complex activity

6. Preparation of crude mitochondrial fraction from rat whole brain homogenate

Complex-1 activity (NADPH dehydrogenase), complex-II activity (succinate dehydrogenase/ SDH), complex IV activity (cytochrome oxidase), complex-V activity (ATP synthase)

7. Estimation of biochemical parameters in serum

advances observed in modern medicine in recent decades, plants still make an important contribution to health care. Medicinal plants are distributed worldwide, but they are most abundant in tropical countries. Over the past decade, interest in drugs derived from higher plants, especially the phototherapeutic ones, has increased expressively. It is estimated that about 25% of all modern medicines are directly or indirectly derived from higher plants. Phytomedicines are standardized herbal preparation consisting of complex mixtures of one or more plants which are used in most countries for the management of various diseases. Other characteristics of phytochemicals are their wide therapeutic use and great acceptance by the population. In contrast to modern medicines, phytochemicals are frequently used to treat chronic diseases. Phytochemicals are normally marketed as standardized preparations in the form of liquid, solid, or various preparations. Compared with well-defined synthetic drugs,

Neuroprotective Strategies of Blood-Brain Barrier Penetrant "Forskolin" (AC/cAMP/PKA/CREB Activator)…

http://dx.doi.org/10.5772/intechopen.80046

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phytochemicals exhibit some marked differences, namely:

• They usually cost less than synthetic drugs

6. Medicinal properties of forskolin

5. Forskolin (Coleus forskohlii)

• The empirical use in folk medicine is a very important characteristic.

treating mood disorders and its anticancer activities is well known.

• They have a wide range of therapeutic use and are suitable for chronic treatments.

• The occurrence of undesirable side effects seems to be less frequent with herbal medicines, but well-controlled randomized clinical trials have revealed that they also exist.

Coleus forskohlii known as phashana bedi (Telugu) a medicinal plant found in the Indian subcontinent is widely used in the Indian system of medicine. Forskolin (FSK) (also known as Colonels) is labdane diterpene that is obtained from the tuberous roots of Coleus forskohlii, which belongs to the family of Lamiaceae. Coleus Forskohlii is one of the world's most researched plant in which FSK is believed to be the plant's most active constituent. C. forskohlii has been used as an important folk medicine in India. C. forskohlii is a perennial herb and grows wild in arid and semi-arid regions of India, Nepal and Thailand; the roots have long been used in Ayurvedic medicine [50]. In traditional medicine, C. forskohlii is commonly used in different countries for various health disorders including cardiovascular diseases, hypertension, asthma, glaucoma and Alzheimer's disease. Its further use in promoting lean body mass,

Traditionally, the roots have been used as condiments in pickles, for preparation of pickles. Forskolin has positive effect against a wide range of conditions such as asthma, glaucoma, hypertension, hair loss, cancer, and obesity [51]. C. forskohlii extract (standardized to contain 95% forskolin) is potentially useful in skin care formulations, particularly as a conditioning age. In traditional Indian systems of medicine, the roots of C. forskohlii are used as a tonic. Other therapeutically relevant properties include anthelmintic action and efficacy in the

Figure 3. Proposed experimental design: propionic acid-induced behavioral and biochemical estimations.

Estimation of complete blood count (CBC) such as determination of different hematological parameters, such as red blood cells (RBC), white blood cells (WBCs), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), neutrophils%, lymphocytes%, monocytes%, eosinophil's%, basophils%, mean platelet volume (MPV), platelet distribution width (PDW)%, plateletcrit (PCT)% and platelets (PLTs) was measured in rat serum or blood sample

#### 8. Miscellaneous

Estimation of blood glucose levels, triglycerides levels, total cholesterol levels, serum C-reactive protein (CRP) levels

9. Inflammatory parameters in tissue homogenate-enzyme-linked immunosorbent assay (ELISA)

Estimation of TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10)

